The DOI matches its Crossref record; 135 of the 135 references it cites were found in a registry or an index; 134 of the 173 sources its claims cite were checked for support.
The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders
Open accessAbstract
Over 40% of the human genome is composed of retrotransposons, DNA species that hold the potential to replicate via an RNA intermediate and are evolutionarily related to retroviruses. Retrotransposons are most studied for their ability to jump within a genome, which can cause DNA damage and novel insertional mutations. Retrotransposon-encoded products, including viral-like proteins, double-stranded RNAs, and extrachromosomal circular DNAs, can also be potent activators of the innate immune system. A growing body of evidence suggests that retrotransposons are activated in age-related neurodegenerative disorders and that such activation causally contributes to neurotoxicity. Here we provide an overview of retrotransposon biology and outline evidence of retrotransposon activation in age-related neurodegenerative disorders, with an emphasis on those involving TAR-DNA binding protein-43 (TDP-43) and tau. Studies to date provide the basis for ongoing clinical trials and hold promise for innovative strategies to ameliorate the adverse effects of retrotransposon dysregulation in neurodegenerative disorders.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review argues that retrotransposons and endogenous retroviruses are activated in age-dependent neurodegenerative disorders and that this activation causally contributes to neurotoxicity, with the strongest evidence in TDP-43 and tau proteinopathies. The authors propose that TDP-43 and tau are distinct upstream triggers converging on retrotransposon dysregulation, a shared node that could be targeted therapeutically (e.g., with reverse transcriptase inhibitors now in clinical trials).
Key findings
- Retrotransposons occupy over 40% of the human genome; the genome contains over half a million LINE elements, of which over 100 human-specific LINE1Hs are replication competent, and millions of SINE and SVA elements, some retaining mobilization potential when LINE-1 reverse transcriptase is present.
- In the largest ALS study cited, RNA-seq of 148 postmortem motor cortex samples was stratified by machine learning into three subtypes: one defined by retrotransposon expression (~20% of samples, with the highest TDP-43 target misexpression and highest TDP-43 pathology), one by glial activation (~20%), and one by oxidative/proteotoxic stress (~60%).
- Retrotransposon activation is reported in AD and PSP brains (particularly HERV class), correlates with tau but not amyloid-beta pathology burden, and is conserved across tau transgenic Drosophila and mouse models; HERV-K ENV expression alone causes neurite retraction in cultured human neurons and progressive motor dysfunction, motor cortex neuronal volume loss, muscle atrophy, and spinal anterior horn degeneration in transgenic mice.
- In Drosophila, glial RNAi knockdown of the mdg4-ERV ameliorates TDP-43-induced reductions in life span, glial and neuronal death, and DNA damage; the NRTI 3TC reduces tau-induced retrotransposition and neurodegeneration, and NRTIs reduce TDP-43 toxicity.
Methods
- Narrative review (Annual Review of Neuroscience) synthesizing human postmortem tissue, blood/CSF biomarker, cell culture, Drosophila, mouse, and organoid studies, organized by protein pathology (TDP-43 vs. tau) rather than clinical diagnosis.
- Includes a summary table (Table 1) of adult age-associated neurodegenerative disorders linked to transposable element dysregulation (ALS/FTD, AD, sporadic CJD, Huntington's disease, Parkinson's disease, PSP), listing human data references and ClinicalTrials.gov IDs with trial phases.
- No primary data collection or new statistical analysis; the paper reviews and interprets existing literature.
Limitations
- Stated by the authors: it remains to be seen whether retrotransposon activity affects relevant clinical outcomes; piRNA biogenesis pathways have not been established in the brain and piRNA-like sequences have not been shown to load onto Piwi protein; the role of piRNAs in the brain remains controversial; it is unclear whether ALS retrotransposon subtypes represent distinct disease forms, stages, or a combination; early repetitive-read analyses had small sample sizes; it is unknown whether tau-induced retrotransposons form eccDNA, whether astrocytic dsRNA is endogenous or taken up, and whether pathological TDP-43 is transferred with viral particles or whether particle movement alone reinitiates pathology.
- Evident from the text: the review is a synthesis of others' work with no new data; the authors disclose serving on the scientific advisory board of Transposon Therapeutics, Inc., and B.F. had a sponsored research agreement with that company, a potential conflict of interest relevant to the therapeutic framing; one cited follow-up study (Mayer et al. 2018) failed to confirm elevated HERV-K expression in ALS cortical samples, and Prudencio et al. (2017) did not detect a positive correlation between TDP-43 pathology burden and retrotransposon expression, so the human evidence is not fully consistent.
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Claims the paper makes
52 Partly supported · 38 Supported · 27 Own interpretation · 15 Sources not found · 10 No basis given · 2 Not supported · 2 Couldn’t confirm · 2 No full text of the sources · 2 Own method · 1 Supported so far · 1 Not checked yet · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Prudencio et al. (2017) did not, however, detect a positive correlation between TDP-43 protein pathology burden and retrotransposon expression.”
What the sources say
- Disputedcites Prudencio et al. 2017 sourceExperimental — accuracy not yet measured
The Results section (‘Accumulation of repetitive elements does not associate with TDP-43’) reports a significant, though mild, positive correlation between pTDP-43 protein levels and repetitive-element transcript expression. The correlation disappeared after adjustment for disease duration, age at death, C9orf72 genotype, and disease subtype. Thus the paper did detect a positive correlation initially, contrary to the claim as stated. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
Every source the paper cites for this claim was checked and supports it.
In the paper
“a subset of human retrotransposons are mobilization competent”
What the sources say
- Supportedcites Brouha et al. 2003 source
The Abstract states that although most human L1 retrotransposons are inactive, some remain retrotransposition-competent. The Discussion reports that 49% of the tested L1s showed retrotransposition activity, directly supporting the claim that a subset is competent. (LLM, conf=0.94)
- Supportedcites Sudmant et al. 2015 source
In “Construction of our phase 3 SV release” (page not provided), the paper reports 16,631 human mobile-element insertions, including Alu, L1 and SVA elements. Those observed insertions support the broad claim that some human retrotransposons can mobilize; the paper does not identify which individual copies are competent. (LLM, conf=0.85)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Retrotransposon-encoded products, including viral-like proteins, double-stranded RNAs, and extrachromosomal circular DNAs, can also be potent activators of the innate immune system.”
What the sources say
- Could not verifycites Chuong et al. 2016 sourceExperimental — accuracy not yet measured
The Abstract describes endogenous retroviruses as sources of IFN-inducible enhancers that regulate immune genes, not as producers of molecules that activate innate immunity. Searches for viral-like proteins, double-stranded RNA, extrachromosomal circular DNA, and retrotransposon products did not locate a passage addressing the claimed activation mechanism. No page number is available in our copy. (LLM, conf=0.75)
- Partly supportedcites Jönsson et al. 2021 sourceExperimental — accuracy not yet measured
The Results section (“ERV-derived proteins are found in areas of microglia activation”; page unavailable) says ERV-derived double-stranded RNA can activate innate immunity. The Discussion (page unavailable) proposes ERV-derived proteins as a possible cause of inflammation, but does not establish that mechanism; our copy does not address extrachromosomal circular DNA as an immune activator. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Among these neurodegenerative disorders, those featuring TAR-DNA binding protein-43 (TDP-43) or tau proteinopathy are where the evidence is strongest”
What the sources say
- Partly supportedcites Copley & Shorter 2023 sourceExperimental — accuracy not yet measured
The sections on ALS/FTD and AD/tauopathy (pages not provided) describe substantial evidence linking transposable elements to TDP-43 and tau pathology. The review does not rank those disorders against other neurodegenerative disorders or say that the evidence for retrotransposon involvement is strongest in them. (LLM, conf=0.82)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Although one follow-up study (Mayer et al. 2018) was unable to confirm elevated HERV-K expression in cortical samples from ALS subjects”
What the sources say
- Supportedcites Mayer et al. 2018 source
The Results section (Quantification of HERV-K(HML-2) transcript levels in ALS and control tissues by RT-qPCR) reports no significant difference in HML-2 transcript levels between ALS and control samples within tissue types. The samples included motor and occipital cortex, supporting the claim about cortical samples. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Genetic perturbations to TDP-43 consistently cause increased expression of retrotransposons.”
What the sources say
- Not matchedcites Li et al. 2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites Romano et al. 2020 sourceExperimental — accuracy not yet measured
The Results section (‘The lack of TBPH induces the expression of retrotransposons in Drosophila’; page unavailable) reports increased accord and gypsy expression in two null alleles of the fly TDP-43 homolog, with genetic rescue reversing their activation. The Discussion also describes retrotransposon activation in a fly model overexpressing human TDP-43. These findings support an association for the perturbations described, but not the unqualified assertion that genetic perturbations to TDP-43 consistently increase retrotransposon expression. (LLM, conf=0.82)
- Partly supportedcites Liu et al. 2019 sourceExperimental — accuracy not yet measured
In Results, “Loss of TDP-43 Increases Retrotransposition Activity” (page unavailable), two TARDBP knockout guides increased LINE1-GFP retrotransposition in HeLa cells. The assay measures retrotransposition, not retrotransposon expression; the paper does not establish that genetic perturbations to TDP-43 consistently increase expression across perturbations or retrotransposons. (LLM, conf=0.86)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A conserved feature of aging is the progressive increase in retrotransposon transcript levels, particularly the ERV class of LTR retrotransposons”
What the sources say
- Partly supportedcites De Cecco et al. 2013 sourceExperimental — accuracy not yet measured
The Results (page not provided) report increased Alu and L1 RNA in senescent cells, and the Discussion says retrotransposon expression changes emerge after cells have remained senescent for weeks. The paper studies replicative senescence, not a conserved increase across aging, and the cited passages do not establish a particular increase in ERV-class LTR retrotransposons. (LLM, conf=0.87)
- Not matchedcites De Cecco et al. 2019a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites Jones et al. 2016 sourceExperimental — accuracy not yet measured
The Results section on fat-body function and lifespan reports a normal age-related increase in gypsy mobilization in Drosophila, while the Results section on TE suppression reports increased TE transcript levels in piwi mutants. These are different observations: the paper does not establish a progressive rise in retrotransposon transcripts during normal aging, show that this is conserved across species, or identify ERV-class LTR elements as particularly affected. No page numbers are available in our copy. (LLM, conf=0.83)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Cellular products that are generated over the life cycle of retrotransposon activation are subject to cellular detection and clearance through the innate immune system”
What the sources say
- Partly supportedcites Chuong et al. 2016 sourceExperimental — accuracy not yet measured
The paper’s AIM2 discussion (section labeled Abstract; page unavailable) describes innate detection of cytoplasmic DNA from bacteria and viruses and an ensuing inflammatory response. It does not say that products generated during retrotransposon activation are detected or cleared by the innate immune system. (LLM, conf=0.78)
- Partly supportedcites Jönsson et al. 2021 sourceExperimental — accuracy not yet measured
The Results section ('ERV-derived proteins are found in areas of microglia activation'; page not provided) says ERV-derived nucleic acids can activate innate immune detection. It does not establish that retrotransposon products generally undergo immune clearance; in the studied neural cells, the authors found no detectable interferon response despite ERV activation. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The other two major subtypes of ALS samples were defined by signatures of glial activation (∼20% of samples) or oxidative and proteotoxic stress (∼60% of samples).”
What the sources say
- Supportedcites Tam et al. 2019 source
The Discussion describes three molecular clusters and states that 60% of patient samples had oxidative and proteotoxic stress markers, while 20% showed extensive glial involvement. The Results identify the corresponding ALS-Ox and ALS-Glial groups by those signatures. (LLM, conf=0.95)
plaincorrelationaln = 148- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In each case, retrotransposon expression was found to be elevated in ALS or FTD samples.”
What the sources say
- Not matchedcites Li et al. 2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites Liu et al. 2019 sourceExperimental — accuracy not yet measured
The Discussion reports growing evidence of endogenous retrovirus reactivation in ALS, and the References list a study reporting elevated repetitive-element transcripts in ALS/FTD brain. But this paper’s Results report increased LINE1 DNA content and chromatin accessibility in FTD-ALS neuronal nuclei, not elevated retrotransposon expression; it does not establish that expression was elevated in each of several studies. (LLM, conf=0.77)
- Supportedcites Prudencio et al. 2017 source
The Results section on frontal-cortex samples reports significantly increased expression of repetitive elements, including LINEs and LTR elements, in C9orf72-positive ALS, ALS/FTLD, and FTLD cases compared with C9orf72-negative cases and healthy controls. The increase was specific to the C9orf72-positive groups; the increase in C9orf72-negative cases versus controls was not statistically significant. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“a third study from the Lee group (Liu et al. 2019) found a direct correlation between TDP-43 pathology and LINE-1 activation”
What the sources say
- Partly supportedcites Liu et al. 2019 sourceExperimental — accuracy not yet measured
The Results section reports significantly more LINE1 DNA in neuronal nuclei lacking TDP-43, and the Discussion reports greater LINE1 chromatin accessibility with TDP-43 pathology. But the Discussion describes increased transposon activity as a possibility, not a directly established correlation between pathology and LINE1 activation in human brain tissue. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Several substantially larger studies have since confirmed the broad upregulation of retrotransposon sequences in subjects with ALS or FTD”
What the sources say
- Partly supportedcites Liu et al. 2019 sourceExperimental — accuracy not yet measured
The Results (page unavailable) report increased LINE1 DNA content in TDP-43-negative neuronal nuclei from seven FTD/ALS cases. The Discussion reports enhanced LINE1 chromatin accessibility but describes increased transposon activity as a possibility. The paper does not establish broad upregulation of retrotransposon sequences or confirm it through several substantially larger studies. (LLM, conf=0.85)
- Partly supportedcites Prudencio et al. 2017 sourceExperimental — accuracy not yet measured
The Results section reports increased repetitive-element transcripts across several classes in C9orf72-positive ALS, ALS/FTLD, and FTLD cases, validated in a larger cohort. But the increase was significant relative to C9orf72-negative cases and controls; the increase in C9orf72-negative cases was not statistically significant. This source therefore supports the finding for a defined subgroup, not broadly for all subjects with ALS or FTD. (LLM, conf=0.88)
- Partly supportedcites Tam et al. 2019 sourceExperimental — accuracy not yet measured
The Results (‘Evidence for Distinct Molecular Subtypes in ALS Patient Samples’; page not provided) report elevated LINE, SINE and LTR expression in 29 of 148 ALS samples, with validation in an independent ALS cohort. This supports upregulation of multiple retrotransposon classes in some people with ALS, but the paper does not establish it broadly across ALS or FTD subjects, nor does this single study substantiate ‘several substantially larger studies.’ (LLM, conf=0.87)
plaincorrelationaln = 148- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Retrotransposon-derived eccDNA ( Figure 2a ) and dsRNA ( Figure 2b ) can initiate an antiviral response through their detection by the cytosolic DNA–sensing pathway mediated by cGAS-STING and nucleic acid–sensing Toll-like receptors (TLRs), as well as viral RNA sensors such as retinoic acid–inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5, a RIG-I-like receptor),”
What the sources say
- Not matchedcites De Cecco et al. 2019a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites Di Giorgio & Xodo 2022 sourceExperimental — accuracy not yet measured
The “ERVs Intracellular Sensing and Signaling” section identifies TLR3 as a dsRNA sensor, cGAS as a cytoplasmic DNA sensor, and RIG-I-like receptors as sensors of retroviral dsRNA. The “dsRNA Detection” section links repetitive-element dsRNA to MDA5 activation and a type I interferon response. The paper does not specifically identify retrotransposon-derived eccDNA as a cGAS-STING trigger, so that part of the claim is not supported. (LLM, conf=0.87)
- Partly supportedcites Gamdzyk et al. 2020 sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says LINE-1-derived cytoplasmic DNA can activate cGAS–STING and that STING activation leads to inflammatory cytokine production. It does not identify that DNA as eccDNA or address retrotransposon-derived dsRNA sensing by TLRs, RIG-I, or MDA5. Type I interferon production is not established by the cited passages beyond the titles in its references. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The few cases of C9orf72 familial ALS were neither enriched nor depleted from the group that was defined by retrotransposon expression.”
What the sources say
- Partly supportedcites Tam et al. 2019 sourceExperimental — accuracy not yet measured
In Results, “Clinical Parameter Association with ALS Subtype” (page not provided), the paper reports that C9orf72 repeat-expansion carriers were neither significantly over- nor underrepresented in the ALS-TE group. It does not establish that those carriers were specifically familial ALS cases; it notes that C9orf72 expansions occur in both familial and sporadic ALS. (LLM, conf=0.85)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Using neuronal nuclei from motor cortex samples of FTD subjects, Liu et al. (2019) found that TDP-43 pathology is associated with chromosome decondensation around LINE-1 elements.”
What the sources say
- Partly supportedcites Liu et al. 2019 sourceExperimental — accuracy not yet measured
The Results report that neuronal nuclei from post-mortem FTD-ALS brains were used to examine TDP-43 pathology, and the Discussion says that pathology was associated with decompaction of LINE chromatin. However, the Methods identify the sampled region as middle frontal neocortex, not motor cortex; that location in the claim is unsupported. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The mdg4-CLEVR reporter reveals that pan-glial TDP-43 overexpression causes mdg4 transposition in astrocyte-like cells as well as perineural and subperineural glia, specialized glial cell types that constitute the Drosophila blood-brain barrier”
What the sources say
- Not matchedcites Chang et al. 2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites Freeman 2015 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
Every source the paper cites for this claim was checked and supports it.
In the paper
“such conditions trigger non-cell-autonomous effects that cause nearby neurons to die”
What the sources say
- Supportedcites Chang & Dubnau 2019 source
The Introduction states that focal hTDP-43 expression in glia causes non-cell-autonomous toxicity that kills adjacent neurons in the Drosophila model. The Discussion likewise describes cell-lethal propagation from affected glia to surrounding neurons. The claim is supported for these experimental conditions. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“RNA interference–mediated glial knockdown of mdg4-ERV is sufficient to ameliorate the negative effects of TDP-43 on life span, glial cell death, accumulation of DNA damage in glia and nearby neurons, and neuronal death”
What the sources say
- Partly supportedcites Chang & Dubnau 2019 sourceExperimental — accuracy not yet measured
The Results section, “Glial hTDP-43 Toxicity to Neurons Is Mediated by the Gypsy ERV and by DNA Damage Signaling” (page unavailable), reports that glial gypsy-IR knockdown reduced glial and neuronal cell-death markers and cell loss. The Introduction reports that blocking gypsy expression extended lifespan in an earlier study. The paper observes DNA damage in glia and nearby neurons, but the passages found do not show that gypsy knockdown reduced that damage; it calls the targeted ERV gypsy rather than establishing the name mdg4-ERV. (LLM, conf=0.86)
- Partly supportedcites Krug et al. 2017 sourceExperimental — accuracy not yet measured
In Results, “RTE and Chk2 activity mediate effects of hTDP-43 on lifespan and cell death” (Figs. 4–5), glial gypsy RNAi partially rescues lifespan and significantly reduces TUNEL-positive nuclei in the CNS. The passages do not show that this knockdown reduces DNA damage in glia or nearby neurons, or distinguish rescued glial from neuronal cell death. DNA damage is discussed as a likely mechanism rather than measured as a knockdown-rescue outcome. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Findings from Drosophila and mouse models of TDP-43 pathology can be generalized to human TDP-43 proteinopathies.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“This is associated with reduced expression of Stathmin-2 (STMN2) and POLDIP3α, two established targets of TDP-43.”
What the sources say
- Supportedcites Chang & Dubnau 2023 source
The Results section (‘Human HERV-K and Drosophila gypsy-ERV…’) reports that HERV-K-driven pathological pTDP-43 accumulation in SH-SY5Y cells is associated with reduced STMN2 and POLDIP3α expression, and identifies both as established TDP-43 targets. (LLM, conf=0.95)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the Feiguin group (Romano et al. 2020) demonstrated that knockout of TBPH, the Drosophila ortholog of TDP-43, triggers retrotransposon expression during larval development”
What the sources say
- Partly supportedcites Romano et al. 2020 sourceExperimental — accuracy not yet measured
The Results section, “The lack of TBPH induces the expression of retrotransposons in Drosophila” (page unavailable), reports increased accord and gypsy expression in TBPH-null flies, establishing the core claim. But that expression analysis used adult heads. The paper also examines TBPH-null larvae, without clearly establishing in our copy that the reported increase in retrotransposon expression occurred during larval development. (LLM, conf=0.84)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Progression of TDP-43 proteinopathies involves non-cell-autonomous signaling among multiple cell types, including astrocytes, microglia, and neurons (Clarke & Patani 2020, Izrael et al. 2020, Vahsen et al. 2021).”
What the sources say
- Partly supportedcites Clarke & Patani 2020 sourceExperimental — accuracy not yet measured
The TARDBP section describes interactions between neuronal TDP-43 and microglia in an ALS mouse model. The ‘Microglial interactions with other cell types in ALS > Astrocytes’ section describes astrocyte–microglia crosstalk and non-cell-autonomous motor-neuron death in ALS, but its specific examples concern SOD1 models, not TDP-43 proteinopathies. The source therefore supports the cellular-interaction premise, but not the claim that signaling among all three cell types drives progression of TDP-43 proteinopathies generally. (LLM, conf=0.84)
- Partly supportedcites Izrael et al. 2020 sourceExperimental — accuracy not yet measured
In “Role and Therapeutic Potential of Astrocytes in ALS” (page unavailable), the review reports TDP-43 pathology spreading between motor neurons and astrocytes and describes astrocyte-mediated effects on neurons. “Other Strategies Targeting Astrocytes Activity” (page unavailable) discusses astrocyte–microglia signaling in ALS, but does not link that signaling specifically to progression of TDP-43 proteinopathies. The claim combines these findings more broadly than the source supports. (LLM, conf=0.86)
- Partly supportedcites Vahsen et al. 2021 sourceExperimental — accuracy not yet measured
The TDP-43 models section (pp. 13, 20) describes microglia-dependent toxicity in co-culture and progressive non-cell-autonomous motor-neuron loss in rats expressing mutant TDP-43 in astrocytes, accompanied by microglial activation. It also says whether microglia actively contribute to disease pathogenesis or merely respond to neuronal damage remains unresolved. These ALS-model findings support interactions among the named cell types, but not the broader assertion that signaling among all three drives progression of TDP-43 proteinopathies generally. (LLM, conf=0.83)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“there also is evidence that HERV-K RNA may drive inflammatory responses via the activation of Toll-like receptors”
What the sources say
- Supportedcites Dembny et al. 2020 source
The Results report that HERV-K RNA caused microglia and macrophages to release proinflammatory molecules, including TNF-α, and that the response required mTlr7 and MyD88. The Introduction (p. 2) also states that HERV-K(HML-2) RNA activates human TLR8 and murine Tlr7 and induces an inflammatory response in microglia. (LLM, conf=0.94)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“But unlike infectious prion diseases (Carlson & Prusiner 2021), intercellular spread of injected pathological TDP-43 has not been found to be sufficient to drive neurodegenerative effects leading to death of recipient cells or to neurological decline.”
What the sources say
- Supportedcites Carlson & Prusiner 2021 source
The citation is attached to the comparison with infectious prion diseases, not to the finding about TDP-43. The Introduction identifies PrP prion diseases as infectious neurodegenerative diseases, and Section 8 says PrP prions spread between cells and can be transmitted by inoculation. Page numbers were not available in our copy. (LLM, conf=0.91)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Overexpression of human TDP-43 in Drosophila causes the broad upregulation of many different groups of retrotransposons”
What the sources say
- Supportedcites Krug et al. 2017 source
The Results section, “Neuronal or glial expression of hTDP-43 induces RTE expression” (page not provided), reports elevated expression of numerous retrotransposons after human TDP-43 expression in Drosophila. It identifies both LINE and LTR retrotransposons, while noting that some responses differ between neuronal and glial expression. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Expression of HERV-K in SH-SY5Y human neuroblastoma cells is sufficient to trigger nuclear clearance of TDP-43 and accumulation of hyperphosphorylated pathological TDP-43 in the cytoplasm (Chang & Dubnau 2023).”
What the sources say
- Supportedcites Chang & Dubnau 2023 source
The Results section, in the subsection on HERV-K and mdg4-ERV, reports that HERV-K expression in SH-SY5Y human neuroblastoma cells increased cytoplasmic TDP-43 phosphorylated at pathological residues S409/410. It also reports cytoplasmic mislocalization and concludes that HERV-K expression is sufficient to redistribute TDP-43 from the nucleus to the cytoplasm. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Neuron-to-neuron transfer has also been observed in vivo in response to injection of aggregated human TDP-43 into the cortex of mice that express pan-neuronal human TDP-43 that is already mislocalized to the cytoplasm (Porta et al. 2018).”
What the sources say
- Partly supportedcites Porta et al. 2018 sourceExperimental — accuracy not yet measured
The Results section ('FTLD-TDP brain extracts seed cytoplasmic TDP-43 in vivo'; page not provided) reports that patient-derived extracts containing pathological TDP-43 were injected into mice expressing cytoplasmic human TDP-43, with the neocortex among the injection sites. The Discussion describes the subsequent spread as consistent with transneuronal transmission, rather than direct observation of neuron-to-neuron transfer. The mice expressed the transgene in forebrain neurons, not pan-neuronally, and injections also targeted the hippocampus and thalamus. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“TDP-43 knockdown in HeLa (Liu et al. 2019) or human SH-SY-5Y neuroblastoma cells also elevates retrotransposon expression (Tam et al. 2019).”
What the sources say
- Partly supportedcites Liu et al. 2019 sourceExperimental — accuracy not yet measured
The Results section, “Loss of TDP-43 Increases Retrotransposition Activity” (page unavailable), reports that CRISPR/Cas9 knockout of TDP-43 in HeLa cells significantly increased LINE1 retrotransposition in a GFP reporter assay. It does not establish that TDP-43 knockdown elevated endogenous retrotransposon expression. The SH-SY-5Y portion of the citing sentence is attributed to Tam et al., not to this paper. (LLM, conf=0.87)
- Supportedcites Tam et al. 2019 source
The Results section, “TDP-43 Functions to Silence Retrotransposons” (page unavailable), reports that all significantly altered retrotransposon transcripts were upregulated after TDP-43 knockdown. The Methods section (page unavailable) identifies the knockdown cells as human SH-SY5Y cells. The HeLa portion of the citing sentence is attributed to Liu et al., not to Tam et al. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“work in Drosophila from the Dubnau group (Chang & Dubnau 2019, 2023; Krug et al. 2017) suggests that the mdg4-ERV is necessary to mediate the toxic impacts of pathological TDP-43”
What the sources say
- Partly supportedcites Chang & Dubnau 2019 sourceExperimental — accuracy not yet measured
The Results section, “Glial hTDP-43 Toxicity to Neurons Is Mediated by the Gypsy ERV and by DNA Damage Signaling” (page unavailable), reports that knocking down gypsy ERV reduced glial and neuronal cell death in the Drosophila model. This supports a mediating role, but the paper describes gypsy as contributing to toxicity; reduced cell death does not establish that it is necessary for all toxic impacts of pathological TDP-43. The cited passages call the element gypsy ERV, not mdg4-ERV. (LLM, conf=0.86)
- Partly supportedcites Krug et al. 2017 sourceExperimental — accuracy not yet measured
The Results section (“RTE and Chk2 activity mediate effects of hTDP-43 on lifespan and cell death”; page unavailable) reports that suppressing the gypsy ERV substantially ameliorated toxicity from glial hTDP-43. But the rescue was partial, with no lifespan rescue when hTDP-43 was expressed in neurons. The paper therefore supports a causal contribution in glia, not the broader claim that this ERV is necessary for TDP-43 toxicity generally; the passages identify it as gypsy rather than mdg4. (LLM, conf=0.88)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Findings from Drosophila and mouse models of TDP-43 pathology can be generalized to human TDP-43 proteinopathies.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The accumulation of pathological protein is detected in some pyramidal neurons in cortical regions that are contralateral to the site of injection.”
What the sources say
- Partly supportedcites Porta et al. 2018 sourceExperimental — accuracy not yet measured
The Results section, “FTLD-TDP brain extracts seed cytoplasmic TDP-43 in vivo” (page unavailable), reports pTDP-43 inclusions in scattered cortical neurons contralateral to the injection site. It identifies pyramidal neurons with aggregates in hippocampal CA1, but does not identify the affected contralateral cortical neurons as pyramidal. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Similarly, mdg4-ERV expression in Drosophila S2 cells triggers the accumulation of cytoplasmic inclusions of hyperphosphorylated human TDP-43 (Chang & Dubnau 2023).”
What the sources say
- Supportedcites Chang & Dubnau 2023 source
The Results section on HERV-K and mdg4-ERV in cultured cells states that mdg4 expression triggers cytoplasmic accumulation of pathologically phosphorylated human TDP-43 in Drosophila S2 cells. It also reports cytoplasmic puncta and insoluble pTDP-43 aggregates. The supplied passages do not give a page number. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Pathogenic forms of tau spread toxicity between cells through a prion-like mechanism involving seeded conformational change (Colin et al. 2020, Frost et al. 2009).”
What the sources say
- Partly supportedcites Colin et al. 2020 sourceExperimental — accuracy not yet measured
The “Tau seeding” section says abnormal tau can convert normal proteins into a pathological form, and “Tau uptake/transfer” describes experimental cell-to-cell transfer and seeding in receiving cells. The paper supports prion-like propagation of tau pathology, but it does not establish that toxicity itself spreads between cells; it also notes that active cell-to-cell transfer has not been visualized in the human brain. The supplied passages have no page numbers. (LLM, conf=0.84)
- Partly supportedcites Frost et al. 2009 sourceExperimental — accuracy not yet measured
The Abstract and Discussion report that extracellular tau aggregates seed intracellular tau misfolding and that newly aggregated tau transfers between co-cultured cells. The Discussion says it remains uncertain whether transferred aggregates induce further aggregation in recipient cells; the study also does not demonstrate that toxicity spreads between cells. The claim presents those steps as an established mechanism. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The endogenous murine leukemia virus was found to potently increase spreading of Sup35 and tau between cells.”
What the sources say
- Supportedcites Liu et al. 2023 source
The Introduction (page unavailable) says reactivation of endogenous MLVs strongly increases intercellular transmission of aggregates and describes transfer of NM yeast-prion and Tau aggregates. The Results (page unavailable) identify NM as a domain of Sup35 and report increased Tau aggregate induction in recipient cells after donor cells expressed MLV proteins. (LLM, conf=0.92)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Studies in tau transgenic Drosophila suggest that TEs are indeed capable of full retrotransposition.”
What the sources say
- Supportedcites Sun et al. 2018 source
The Results section, “Active transposable element mobilization in neurons of tau transgenic Drosophila” (page unavailable), describes a reporter designed to detect retrotransposon insertion and reports significantly increased mobilization in adult tau-transgenic flies. This supports the claim that the elements are capable of completing retrotransposition. (LLM, conf=0.90)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“This non-cell-autonomous propagation of TDP-43 pathology requires the expression of the mdg4-ERV in glia.”
What the sources say
- Supportedcites Chang & Dubnau 2023 source
The Results section headed “mdg4-ERV expression in SPG is required to trigger neuronal pTDP-43” directly supports the claim. In the Drosophila experiment, knocking down mdg4-ERV in SPG glia significantly attenuated the non-cell-autonomous appearance of pTDP-43 in surrounding neurons. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Retrotransposons with elevated DNA copy numbers were first identified in brains of tau transgenic Drosophila (Guo et al. 2018).”
What the sources say
- Supportedcites Guo et al. 2018 source
The Results section reports modest but significant Tau- and age-dependent increases in retrotransposon copy number measured in genomic DNA from adult fly heads. The Discussion identifies copia, gypsy, and het-a as the elements with increased copy number; it cautions that this does not establish retrotransposition. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Overexpression of human TDP-43 in Drosophila surface glia results in the accumulation of hyperphosphorylated human TDP-43 in nearby neurons, even though the neurons only express physiological levels of human TDP-43 (Chang & Dubnau 2023).”
What the sources say
- Supportedcites Chang & Dubnau 2023 source
The Results section, “Intercellular propagation of human TDP-43 proteinopathy in a Drosophila in vivo model,” states that TDP-43 was overexpressed in subperineurial glia while surrounding neurons expressed human TDP-43 at physiological levels. It reports nuclear and cytoplasmic pathological phosphorylated TDP-43 in those neurons after glial induction, with no such accumulation in controls. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“While it is currently unknown whether Arc1 mediates neurotoxicity in the context of TDP-43 proteinopathy, Arc1 transcript levels are also highly elevated in brains of TDP-43 transgenic Drosophila (Krug et al. 2017).”
What the sources say
- Could not verifycites Krug et al. 2017 sourceExperimental — accuracy not yet measured
The Results section on neuronal or glial hTDP-43 expression reports changes in many transcripts in fly head tissue, but does not identify Arc1 among them. Searches for “Arc1 transcript levels” and “Arc1” found no passage in our copy reporting elevated Arc1 expression; the general transcript findings do not establish this gene-specific claim. Page numbers were not available in our copy. (LLM, conf=0.72)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“Overexpression of HERV-W-, -K-, -R-, and -H-encoded ENV glycoproteins was also found to facilitate the spread of tau between cells in coculture.”
What the sources say
- Supportedcites Liu et al. 2023 source
The Results section, “HERV Envelope proteins increase proteopathic seed spreading,” reports increased intercellular Tau aggregate spreading in HEK-cell cocultures expressing HERV-W or HERV-K Env. The same section says HERV-R and HERV-H envelope proteins were similarly tested and also enhanced intercellular aggregate spreading. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A similar phenomenology underlies the propagation of TDP-43-mediated toxicity from Drosophila glial cells to neurons in vivo.”
What the sources say
- Supportedcites Chang & Dubnau 2023 source
The Results section on intercellular propagation reports that inducing TDP-43 pathology in a subset of Drosophila glia produced pathological changes in nearby neurons that increased with time and distance. The Results section on neuronal DNA damage and loss also reports neuronal damage and gradual neuronal loss after glial TDP-43 induction. The claim concerns propagation of toxicity, not physical transfer of TDP-43 protein. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Pan-neuronal expression of human tau causes dsRNA accumulation in astrocyte-like cells of the Drosophila brain.”
What the sources say
- Supportedcites Ochoa et al. 2023 source
The Results describe a Drosophila model with pan-neuronal expression of human tau carrying the R406W mutation. In the same section, the authors report increased brain dsRNA and enrichment of dsRNA in astrocyte-like glia of the tau-transgenic flies. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Leveraging RNA-seq data from the Accelerating Medicines Partnership–Alzheimer's Disease (AMP-AD) project, the Frost group (Sun et al. 2018) discovered that retrotransposons, particularly of the HERV class, are elevated in brains of patients with AD and progressive supranuclear palsy (PSP), a primary tauopathy, compared to controls.”
What the sources say
- Partly supportedcites Sun et al. 2018 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The activity-regulated cytoskeleton-associated protein ARC, for example, possesses a Gag domain that is thought to have originated from a retrotransposon (Ashley et al. 2018, Pastuzyn et al. 2018).”
What the sources say
- Supportedcites Ashley et al. 2018 source
The Introduction identifies mammalian Arc as containing Gag-like sequences found in retrotransposons. The Discussion section on retroviruses and trans-synaptic transport says mammalian Arc and dArc1 contain viral-like Gag sequences that are likely remnants of an earlier transposon insertion, supporting the claim’s qualified account of their origin. (LLM, conf=0.94)
- Supportedcites Pastuzyn et al. 2018 source
The correction (p. 275) says the study showed homology between Arc and Gag proteins and identifies a Results section on Arc genes originating from Ty3/gypsy retrotransposons. This supports the attributed claim about Arc’s Gag-derived domain and retrotransposon origin. (LLM, conf=0.90)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Using a similar approach that utilized data from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), Shulman and colleagues (Guo et al. 2018) discovered that the elevation of specific HERV transcripts is associated with decreased cognitive performance in the year before death in patients with AD.”
What the sources say
- Partly supportedcites Guo et al. 2018 sourceExperimental — accuracy not yet measured
The Results (page unavailable) report that, in ROSMAP, activation of three endogenous retrovirus clades was related to global cognitive performance in the year proximate to death. The passage does not establish that specific HERV transcripts were associated with decreased performance, and the analyzed cohort is described as deceased ROSMAP participants rather than exclusively patients with AD. (LLM, conf=0.85)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Similarly, tau transgenic mice were found to have an increased DNA copy number of some retrotransposons that are thought to be transpositionally incompetent (Ramirez et al. 2022).”
What the sources say
- Partly supportedcites Ramirez et al. 2022 sourceExperimental — accuracy not yet measured
The Results section reports increased retrotransposon DNA copy number in brains of tau transgenic mice. It also says some NanoString probes detect both active and inactive members, but does not establish that the increased copies specifically belong to transpositionally incompetent retrotransposons; the Discussion notes that the assays cannot distinguish genomic from episomal DNA. (LLM, conf=0.85)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Similar to HERV-K (Contreras-Galindo et al. 2015, Dewannieux et al. 2006, Lee & Bieniasz 2007), Drosophila mdg4 contains a functional Env gene that enables both cell-associated and cell-free viral transmission between cultured S2 cells (Keegan et al. 2021).”
What the sources say
- Supportedcites Keegan et al. 2021 source
The Introduction (page unavailable) reports that gypsy transfers between cultured Drosophila S2 cells by both cell-associated and cell-free routes, and that both require an intact Env open reading frame. The Results section “Intercellular transmission of gypsy requires Env” further shows that deleting Env nearly eliminated cell-free transfer and supplying Env restored it. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Among retrotransposons that are transcriptionally elevated in human AD and PSP, most are no longer active (Guo et al. 2018, Sun et al. 2018).”
What the sources say
- Partly supportedcites Guo et al. 2018 sourceExperimental — accuracy not yet measured
The Discussion (page not provided) reports that none of nine transposable elements with significant tau-associated expression changes were predicted to transpose autonomously, supporting a limited version of the claim for AD. It does not address PSP, and inability to transpose autonomously is not the same as being wholly inactive: the Discussion notes that SINEs can transpose with help from an active L1 element. (LLM, conf=0.86)
- Partly supportedcites Sun et al. 2018 sourceExperimental — accuracy not yet measured
The Results section, “Aberrant transposable element transcription in human tauopathy” (page unavailable), reports elevated transposable-element transcripts in human AD and PSP, with endogenous retroviruses over-represented among those upregulated. It does not say that most of the elevated retrotransposons are no longer active; the passage about mobilization-capable elements concerns Drosophila, not the human samples. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Using a fluorescence-based reporter of de novo TE insertion (Li et al. 2013), Sun et al. (2018) found that pan-neuronal expression of transgenic human tau induced transposition in adult neurons of the Drosophila brain.”
What the sources say
- Not matchedcites Li et al. 2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites Sun et al. 2018 sourceExperimental — accuracy not yet measured
The Results section, “Active transposable element mobilization in neurons of tau transgenic Drosophila” (page unavailable), reports increased mobilization in adult flies using a GFP-based insertion reporter. But it explicitly says the reporter experiment used human tau driven in retinal neurons by GMR, rather than pan-neuronal tau expression. The Methods section, “Drosophila genetics” (page unavailable), confirms that distinction. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In recent years, studies in Drosophila, mice, and humans have suggested that pathogenic forms of tau drive neurodegeneration by activating retrotransposons (Guo et al. 2018, Ochoa et al. 2023, Ramirez et al. 2022, Sun et al. 2018, Wahl et al. 2023).”
What the sources say
- Partly supportedcites Guo et al. 2018 sourceExperimental — accuracy not yet measured
The Results and Discussion report that tau activates retrotransposons in Drosophila and is associated with retrotransposon expression in human brains; the Discussion proposes that this activation could lead to neuronal dysfunction or loss. Guo et al. do not report a tau–retrotransposon study in mice, and they say the causal link to neurodegeneration remains to be established. No page numbers are available in our copy. (LLM, conf=0.87)
- Supportedcites Ochoa et al. 2023 source
The Introduction says recent studies found retrotransposon activation in tau-mediated neurotoxicity, identified elevated retrotransposon RNA in Drosophila, mouse, and human tauopathy, and suggested a causal role in neurodegeneration. The paper’s Drosophila results also link tau-induced retrotransposon-derived dsRNA to neurodegeneration. Page numbers were not provided. (LLM, conf=0.94)
- Supportedcites Ramirez et al. 2022 source
The Introduction reports tau-induced retrotransposon activation in mouse brain, describes fly studies suggesting that this activation drives neurodegeneration, and notes associations in human tauopathies. Together, these passages support the citing sentence’s hedged, collective claim; it does not require this mouse study alone to prove the mechanism. (LLM, conf=0.88)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In tau transgenic Drosophila, the nucleoside analog reverse transcriptase inhibitor (NRTI) 3TC reduces tau-induced retrotransposition and neurodegeneration (Sun et al. 2018).”
What the sources say
- Supportedcites Sun et al. 2018 source
The Results section on reverse-transcriptase inhibition reports that 3TC (lamivudine) is a nucleoside analog inhibitor of reverse transcriptase. In tau transgenic flies, it significantly reduced gypsy-TRAP reporter activation in the brain, a measure of transposable-element mobilization, and significantly reduced tau-induced neuronal death. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In addition to tau-induced decondensation of heterochromatin, brains of tau transgenic Drosophila were found to have significantly decreased levels of Piwi and piRNAs.”
What the sources say
- Supportedcites Sun et al. 2018 source
The Results section on Piwi/piRNA depletion reports significantly decreased piRNAs in heads of tau-transgenic Drosophila and depleted Piwi protein in their brains. The Results section on heterochromatin also describes tau-induced heterochromatin relaxation in Drosophila models. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Recent studies in two mouse models of tauopathy (Vallés-Saiz et al. 2023, Wahl et al. 2023) and in AD model organoids (Sun et al. 2023) also indicate that 3TC suppresses toxicity.”
What the sources say
- Supportedcites Vallés-Saiz et al. 2023 source
This citation supports the tauopathy-mouse-model portion of the sentence, not the separately cited second mouse model or AD organoids. In Results §2.3, 3TC-treated P301S mice had significantly fewer apoptotic cells; the Discussion also reports less neuronal death, brain atrophy, and motor and memory impairment. These findings support the paraphrase that 3TC suppresses toxicity in this model. (LLM, conf=0.93)
- Supportedcites Wahl et al. 2023 source
The Results section (‘3TC improves cognitive function in a mouse model of tauopathy’) reports that 3TC-treated rTg4510 mice performed better on a recognition-memory test than untreated tauopathy mice and showed reduced anxiety responses. This supports the portion of the sentence attributed to Wahl et al.: a protective effect of 3TC in a mouse model of tauopathy. The other mouse model and the organoids are attributed to different citations. (LLM, conf=0.89)
- Not matchedcites Sun et al. 2023
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Studies in Drosophila indicate that the negative effects of tau on the lamin nucleoskeleton result in the decondensation of heterochromatin (Frost et al. 2014) and a toxic, neuroinflammatory activation of retrotransposons (Ochoa et al. 2023, Sun et al. 2018).”
What the sources say
- Partly supportedcites Frost et al. 2014 sourceExperimental — accuracy not yet measured
The Results section on chromatin structure reports reduced heterochromatin markers and diffuse chromocenter labeling in tau-transgenic Drosophila, supporting tau-associated heterochromatin decondensation. The paper does not establish damage to the lamin nucleoskeleton as its cause; the Discussion instead identifies oxidative stress and DNA damage as one mechanism. The retrotransposon claim is attached to other citations, not Frost et al. (LLM, conf=0.85)
- Supportedcites Ochoa et al. 2023 source
Ochoa et al. is cited for the toxic, neuroinflammatory retrotransposon response, not the preceding lamin claim. The Results identify retrotransposon-derived dsRNA in tau transgenic Drosophila, and the Discussion states that this dsRNA drives neuroinflammation and that reducing it ameliorates neurodegeneration. (LLM, conf=0.91)
- Partly supportedcites Sun et al. 2018 sourceExperimental — accuracy not yet measured
The Results sections on Drosophila transposable-element transcripts and loss of silencing support tau-associated retrotransposon dysregulation and neuronal toxicity. The Discussion only speculates that endogenous retroviruses might contribute to neuroinflammation in human tauopathy; it does not establish neuroinflammatory activation in Drosophila. Page numbers were not available in our copy. (LLM, conf=0.88)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A growing body of evidence suggests that retrotransposons are activated in age-related neurodegenerative disorders”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
- Rests on an assumption: Over 40% of the human genome is composed of retrotransposons.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and that such activation causally contributes to neurotoxicity”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Work in animal models also provides some mechanistic insight and evidence for a causal impact of retrotransposons on neurodegeneration.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Findings from Drosophila and mouse models of TDP-43 pathology can be generalized to human TDP-43 proteinopathies.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This section discusses the evidence that retrotransposons contribute causally to disease progression”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
- The authors state this as an assumption: Mechanisms underlying the onset and progression of neurodegeneration are shared primarily based on the type of protein pathologies observed rather than clinical presentation.
In the paper
“This study indicated a broad upregulation of retrotransposon sequences in human subjects as well as in several mouse models”
What the sources say
- Not matchedcites Li et al. 2012
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The connection between TDP-43 protein dysfunction and retrotransposon activation is highly consistent with findings from cell culture and several animal models.”
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Findings from Drosophila and mouse models of TDP-43 pathology can be generalized to human TDP-43 proteinopathies.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“earlier reports of relatively high levels of reverse transcriptase enzymatic activity in blood and cerebrospinal fluid from ALS subjects and blood relatives”
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Generally speaking, retrotransposon surveillance systems in the brain are poorly understood compared to those in the germline.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The past few years have seen a rapid growth in the evidence that retrotransposons play an important role in neurodegenerative disorders involving TDP-43 proteinopathy.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
- The authors state this as an assumption: Mechanisms underlying the onset and progression of neurodegeneration are shared primarily based on the type of protein pathologies observed rather than clinical presentation.
In the paper
“the study nevertheless found evidence for broad dysregulation of LINEs, SINEs, and LTRs/ERVs”
What the sources say
- Not matchedcites Li et al. 2012
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“Transgenic expression of TDP-43 also causes mdg4 transposition.”
What the sources say
- Not matchedcites Chang et al. 2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Among them, mdg4 is one of the most active ERV elements in the fly genome.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Work from the Nath lab (Li et al. 2015) shows that expression of HERV-K, or even just its ENV protein, is sufficient to cause neurite retraction in cultured human neurons.”
What the sources say
- Not matchedcites Li et al. 2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Full-length sequences of HERV-K and mdg-4 contain functional Env genes that could potentially allow the intercellular transmission of viral particles.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the Drosophila mdg4-ERV (also known as gypsy, but herein referred to as mdg4) is induced from glial, but not neuronal, TDP-43 expression”
What the sources say
- Not matchedcites Li et al. 2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“HERV-K ENV expression is accompanied by nucleolar stress and accumulation of DNA damage”
What the sources say
- Not matchedcites Li et al. 2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Evidence is also emerging to support the hypothesis that retrotransposons causally mediate TDP-43-induced toxicity.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Transgenic overexpression of the HERV-K ENV protein is thus sufficient to drive motor neuron toxicity in mice, reminiscent of the effects in ALS subjects”
What the sources say
- Not matchedcites Li et al. 2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Findings from Drosophila and mouse models of TDP-43 pathology can be generalized to human TDP-43 proteinopathies.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, these findings suggest that ERV expression can cause pathological TDP-43 to accumulate in the glia where the ERV is expressed and in nearby neurons.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“While it is currently unknown whether retrotransposon-encoded protein contributes to neurotoxicity in tauopathy, the sufficiency of HERV-K or HERV-K-encoded ENV to drive motor neuron disease in mice (Li et al. 2015) indicates that retrotransposon-encoded proteins have the potential to be neurotoxic.”
What the sources say
- Not matchedcites Li et al. 2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the case of mdg4, this feedback amplification also underlies intercellular spread.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“ARC protein levels are elevated in postmortem human brain tissue from patients with AD (Wu et al. 2011), and Drosophila Arc1 transcripts (Zuniga et al. 2023) and Arc1 protein multimers (Schulz et al. 2023) are elevated in brains of tau transgenic Drosophila, suggestive of capsid formation.”
What the sources say
- Not matchedcites Wu et al. 2011
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Studies to date overwhelmingly suggest that TE activation in AD is a consequence of pathogenic forms of tau.”
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As recipient cells did not exhibit tau pathology unless donor cells produced tau aggregates, this work strongly suggests that viral-like particles produced from ERVs physically facilitate the spread of tau multimers between cells.”
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“New studies suggest that the feedback between ERV expression and the intercellular spread of TDP-43 may be broadly applicable to other aggregation-prone proteins involved in neurodegenerative disorders, including tau.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Studies in Drosophila have furnished insights into how pathogenic forms of tau induce changes in nuclear and genomic architecture, thus disrupting retrotransposon silencing mechanisms.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There is strong support for the conclusion that retrotransposon activation is a robust feature of TDP-43 and tau proteinopathies that is conserved across model systems and in the human brain.”
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Reverse transcriptase inhibitors would not, in theory, affect the dsRNA or viral-like proteins that are produced as a consequence of retrotransposon activation.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 53
- Probably not a substantial claim. 30
- The quote only partly states this claim. 1
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Human analyses determined that differential retrotransposon expression correlates with the burden of tau, but not Aβ, pathology in AD (Guo et al. 2018).”
What the sources say
- Disputedcites Guo et al. 2018 sourceExperimental — accuracy not yet measured
The Results section supports an association between retrotransposon expression and tau tangle burden. But it also reports that a subset of expression signatures was associated with neuritic amyloid plaques; the Discussion says the amyloid association was weaker, not absent. Thus the claim’s “but not Aβ” distinction is contrary to the paper. (LLM, conf=0.89)
Checked by a reasoning model — may be wrong.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Disputed
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Each of the viral genes are functional in at least one provirus in the genome, providing for the possibility that partially functional viral particles may be produced, or that functional viral particles could be generated by trans-complementation.”
What the sources say
- Partly supportedcites Hohn et al. 2013 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“While most human retrotransposons and all human DNA transposons have lost transpositional ability due to their accumulation of truncations and mutations over the course of evolution”
What the sources say
- Partly supportedcites Brouha et al. 2003 sourceExperimental — accuracy not yet measured
The Abstract states that more than 99.8% of human L1 retrotransposons are inactive because of truncations, rearrangements, and mutations. That supports the claim for L1s, but the paper does not establish it for most human retrotransposons as a whole or for all human DNA transposons. (LLM, conf=0.88)
- Could not verifycites Sudmant et al. 2015 sourceExperimental — accuracy not yet measured
The Construction of our phase 3 SV release section reports mobile-element insertions, and the Discussion mentions retrotransposition, but neither addresses whether most human retrotransposons or all human DNA transposons have lost transpositional ability. Searches for truncations, mutations, and inactive transposons found no passage in our copy supporting the claimed evolutionary explanation. Page numbers were not available in the indexed passages. (LLM, conf=0.76)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Although there are no replication-competent human endogenous retroviruses (HERVs), the human genome contains a number of full-length HERV-K(HML-2) proviruses that each encode several intact open reading frames”
What the sources say
- Partly supportedcites Hohn et al. 2013 sourceExperimental — accuracy not yet measured
The Introduction says all known human proviruses are non-infectious, and the Postintegrational Mutations and Replication Potential of HERV-K section describes HERV-K(HML-2) proviruses with open reading frames for all viral genes. But that section does not rule out an infectious HERV-K(HML-2) provirus of low prevalence, so the claim's unqualified statement that none are replication-competent is stronger than the source. (LLM, conf=0.83)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“There are numerous reports of small RNAs with piRNA length and sequence features being detected in the brain via small RNA sequencing, including in postnatal mouse brain development”
What the sources say
- Partly supportedcites Sato et al. 2023 sourceExperimental — accuracy not yet measured
The Introduction and “Neuronal expression of piRNAs” section (pages unavailable) describe piRNA length and report multiple studies detecting piRNAs in brains. The Introduction links small-RNA discovery generally to next-generation sequencing, but our copy does not establish that the cited brain detections used small RNA sequencing or describe detection during postnatal mouse brain development. (LLM, conf=0.84)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The human genome contains over half a million LINE elements, of which over 100 from the human-specific LINE element subset (LINE1Hs) are replication competent”
What the sources say
- Partly supportedcites Kazazian & Moran 2017 sourceExperimental — accuracy not yet measured
The Retrotransposons section (page unavailable) says each human genome has more than 500,000 LINE-1 sequences, about 100 of which are active. It does not identify those active elements as LINE1Hs or say that more than 100 are replication competent. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“LTR retrotransposons utilize viral-like retrotransposon-encoded products that include capsid, reverse transcriptase, and integrase”
What the sources say
- Supportedcites Wells & Feschotte 2020 source
In “Class I retrotransposons,” the paper says autonomous LTR elements encode gag and pol proteins. Gag-encoded proteins assemble a viral-like particle that encapsidates the RNA, while pol encodes reverse transcriptase and integrase activities. (LLM, conf=0.91)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Engineered recombinant HERV-K constructs that contain all open reading frames are capable of viral transmission in cell culture”
What the sources say
- Partly supportedcites Contreras-Galindo et al. 2015 sourceExperimental — accuracy not yet measured
Materials and Methods describes an infectious engineered HERV-KCON construct, and the Results (Fig. 4B caption) uses its infectivity in 293T cells as a positive control for transmission. The copy does not establish that the transmitted construct retained all open reading frames: it describes a reporter inserted into env and VSV-G-pseudotyped virions. The Bogota reporter used in the main transmission experiments had its retroviral genes replaced. (LLM, conf=0.83)
- Supportedcites Dewannieux et al. 2006 source
The Results describe engineered HERV-K chimeras able to express all retroviral genes and report proviral integration in cultured BHK21 cells after infection with the triple chimera. The finding applies to the infectious construct, not every chimera tested: the K109/K115 chimera was not infectious on its own. Page numbers were not available in our copy. (LLM, conf=0.90)
- Partly supportedcites Lee & Bieniasz 2007 sourceExperimental — accuracy not yet measured
The Results section, “Generation of HERV-KCON–Based Infectious Virions” (page not available), reports infectious transfer in cell culture using engineered HERV-KCON particles. But the infectious construct had a disrupted Env open reading frame and required VSV-G supplied separately. In “HERV-KCON Tropism,” the authors report no detectable infection when they combined HERV-KCON cores with HERV-KCON Env, so the paper does not demonstrate transmission by a construct containing all open reading frames. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“some of these elements retain mobilization potential when LINE-1 reverse transcriptase is present”
What the sources say
- Supportedcites Hancks & Kazazian 2012 source
The Introduction (page not supplied) says that L1 commonly retrotransposes SINEs (Alus) and SVAs, and specifically describes SVAs as mobilized by L1 in trans. This supports the claim that these non-LTR elements can be mobilized using L1 machinery. (LLM, conf=0.91)
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Mammalian species utilize a variety of mechanisms to keep retrotransposon activation in check”
What the sources say
- Supportedcites Di Stefano 2022 source
Section 3, “TE Silencing,” says genomes use a range of mechanisms to silence transposable elements and describes small-RNA-mediated post-transcriptional silencing in mice. Section 4.6 describes transcription factors and chromatin-based repression of retrotransposons in mice and humans. (LLM, conf=0.92)
- Not matchedcites Grassi et al. 2019
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites Janssen et al. 2018 sourceExperimental — accuracy not yet measured
The LINE-1 silencing passage (p. 8.14) describes DNA methylation, Kap1, and H3K9me3 repressing mammalian retrotransposons, supporting the broad statement in the verbatim citing sentence. The expanded claim also specifies posttranscriptional silencing by small RNAs, which the cited passages do not establish for mammals; the Heterochromatin Establishment section says whether the RNAi-dependent mechanism it describes is conserved in mammals remains unresolved. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Piwi and piRNAs are most abundant in the germline, where they play a key role in retrotransposon silencing at the RNA and chromatin levels”
What the sources say
- Not checked — no full text of the sourcecites Brennecke et al. 2007 source
- Partly supportedcites Brower-Toland et al. 2007 sourceExperimental — accuracy not yet measured
The section on PIWI colocalization with HP1a reports that PIWI appears more abundant in prospective germline nuclei, and the Discussion links PIWI to transposon silencing and heterochromatic silencing. Our copy does not establish that piRNAs are most abundant in the germline or that PIWI and piRNAs silence retrotransposons at the RNA level. (LLM, conf=0.84)
- Partly supportedcites Wang & Elgin 2011 sourceExperimental — accuracy not yet measured
The Abstract describes piRNA-mediated posttranscriptional transposon silencing, and the Discussion reports evidence for a chromatin-based mechanism involving germ-line Piwi. However, the paper does not establish that Piwi and piRNAs are most abundant in the germ line; the Abstract also describes Piwi and piRNA pathways in the ovarian soma. Its findings concern transposons, without establishing that both mechanisms apply specifically to retrotransposons. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“The replication mechanism and encoded proteins of LTR retrotransposons are related to those of retroviruses.”
What the sources say
- Supportedcites Wells & Feschotte 2020 source
The Class I retrotransposons section says that LTR elements’ coding capacity and replication mechanisms closely resemble those of retroviruses. It also identifies the gag and pol genes and says retroviral replication and integration are essentially the same as those of LTR elements. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“tau pathology is a defining feature not only of Alzheimer's disease (AD) but also of almost half of FTD cases (typically those without TDP-43 pathology)”
What the sources say
- Partly supportedcites Chornenkyy et al. 2019 sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) identifies tau proteinopathy as an important pathologic hallmark in Alzheimer’s disease and related dementias, and the Genetic pleiotropy section (page unavailable) discusses FTLD-Tau. The copy does not establish that tau pathology occurs in almost half of FTD cases. Its Pathologic cascades and synergies section also describes tau and TDP-43 co-occurring, so it does not establish the claimed typical absence of TDP-43 in those cases. (LLM, conf=0.86)
- Partly supportedcites Karch et al. 2018 sourceExperimental — accuracy not yet measured
The introductory passage under Conclusions and Relevance (page unavailable) identifies tau inclusions as one way FTD subtypes are distinguished from those with TDP-43 inclusions. It does not say that tau pathology occurs in almost half of FTD cases or establish the claim about Alzheimer’s disease. Its 40%–50% figure concerns patients with ALS who have FTD-associated clinical phenotypes, not tau pathology in FTD. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“MAPT mutations drive tau pathology”
What the sources say
- Partly supportedcites Ferrari et al. 2014 sourceExperimental — accuracy not yet measured
The Introduction identifies MAPT mutations as associated with FTD and describes tau pathology in a subset of FTD cases. The Results suggest that excluding known chromosome 17 mutation carriers may help explain the weak MAPT-locus association, but the paper does not establish that MAPT mutations drive tau pathology. (LLM, conf=0.79)
- Not checked — no full text of the sourcecites Hutton et al. 1998 source
- Not checked — no full text of the sourcecites Poorkaj et al. 1998 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“a study from the Petrucelli and Link labs (Prudencio et al. 2017) reported the enrichment of retrotransposon transcripts in a subset of ALS samples from C9orf72 familial disease”
What the sources say
- Supportedcites Prudencio et al. 2017 source
The Discussion reports significant upregulation of repetitive-element transcripts in C9orf72 ALS cases compared with sporadic ALS cases. The Results figure caption identifies upregulated LTR, SINE and LINE elements, which the Introduction classifies as retrotransposons. The paper therefore supports the claim about a subset of ALS samples; the cited passages do not provide page numbers. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“retrotransposon expression has in fact been shown to have a role in DNA damage (Yousefzadeh et al. 2021), cellular senescence (Bussian et al. 2018, De Cecco et al. 2019b, Li et al. 2013, Musi et al. 2018), and inflammatory signaling (Franceschi et al. 2018, Gulen et al. 2023), which are well-described features of both aging and some neurodegenerative disorders”
What the sources say
- Could not verifycites Yousefzadeh et al. 2021 sourceExperimental — accuracy not yet measured
The Yousefzadeh citation is attached specifically to the proposed role of retrotransposon expression in DNA damage. The passages on DNA damage and cellular senescence discuss other sources and consequences of damage, but searches for “retrotransposon” and related terms found no passage connecting retrotransposon expression to DNA damage. (LLM, conf=0.76)
- Could not verifycites Bussian et al. 2018 sourceExperimental — accuracy not yet measured
The main text reports senescent glial cells in a mouse model of tau-dependent neurodegeneration, but does not address whether retrotransposon expression has a role in cellular senescence. Searches for “retrotransposon expression” and “LINE-1 transposable element” found no passage addressing that link. (LLM, conf=0.76)
- Could not verifycites Franceschi et al. 2018 sourceExperimental — accuracy not yet measured
The citation to Franceschi et al. is attached to the claim that retrotransposon expression has a role in inflammatory signaling. The review discusses inflammation triggered by other nucleic acids, including cell-free DNA (Degeneracy of damage sensors, p. 9), but the passages found when searching for retrotransposons and transposable elements do not address that link. (LLM, conf=0.74)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“One subtype, which included about 20% of the samples, was defined by retrotransposon expression, exhibited the highest degree of misexpression of TDP-43 targets, and correlated with the highest levels of TDP-43 protein pathology.”
What the sources say
- Partly supportedcites Tam et al. 2019 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Age-dependent neurodegenerative disorders are clinically diverse but exhibit significant comorbidity and heterogeneous pathology both within and across disorders”
What the sources say
- Supportedcites Chornenkyy et al. 2019 source
The section “Downstream effects” (page unavailable) says that multiple diseases affect aged brains, that different proteinopathies often co-occur in the same brain, and that cognitive impairment is not usually associated with ‘pure’ Alzheimer’s pathology. The “Pathologic cascades and synergies” section (page unavailable) describes Tau and TDP-43 pathology across diverse conditions, supporting the claim’s broad characterization of clinical and pathological diversity. (LLM, conf=0.88)
- Partly supportedcites Ferrari et al. 2014 sourceExperimental — accuracy not yet measured
The Introduction (page not provided) describes distinct clinical forms of frontotemporal dementia, overlap with motor neuron disease and atypical parkinsonian disorders, and heterogeneous molecular pathology. The Discussion (page not provided) also describes FTD’s varied clinical and pathological features. These passages support the claim for FTD, but not its broader assertion about age-dependent neurodegenerative disorders generally or significant comorbidity across them. (LLM, conf=0.87)
- Supportedcites Geser et al. 2010 source
The Introduction (page unavailable) describes neurodegenerative diseases as highly variable in phenotype and states that clinicopathological features overlap across neurodegenerative diseases. The clinico-pathological correlations section (page unavailable) further documents overlapping clinical features and differing pathological subtypes among ALS and FTLD-related disorders. These passages support the claim’s broad characterization. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“It is likely that the effects of TDP-43 on retrotransposon expression are direct because TDP-43 binds directly to retrotransposon RNAs (Li et al. 2012, Tam et al. 2019) and plays a role in silencing retrotransposons at the chromatin level in human cells and in C. elegans”
What the sources say
- Not matchedcites Li et al. 2012
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites Tam et al. 2019 source
The Tam et al. citation is attached to the claim that TDP-43 binds retrotransposon RNAs, not to the subsequent chromatin-level claim. In Results, “TDP-43 Functions to Silence Retrotransposons,” the paper reports eCLIP evidence of direct binding to retrotransposon targets in human cells; the same section reports that retrotransposon transcripts increased after TDP-43 knockdown. (LLM, conf=0.92)
- Partly supportedcites Liu et al. 2019 sourceExperimental — accuracy not yet measured
The Results (page unavailable) report that TDP-43 knockout in human HeLa cells reduced a heterochromatin mark on LINE1 chromatin and increased retrotransposition, supporting a role in chromatin-level suppression. The Introduction reports TDP-43 binding to LINEs, citing Li et al. (2012). Our copy does not show chromatin-level silencing in C. elegans or establish that TDP-43’s effects on retrotransposon expression are direct. (LLM, conf=0.86)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Knockout of the C. elegans tdp1 ortholog or of TDP-43 in human cells also results in dsRNA accumulation, including sequences that map to TEs”
What the sources say
- Partly supportedcites Saldi et al. 2014 sourceExperimental — accuracy not yet measured
The Abstract reports that deletion of worm tdp-1 increases dsRNA, including transposon transcripts. The Results section, “Limiting dsRNA accumulation is a conserved function of human TDP-43,” reports increased dsRNA from the HERV-K retrotransposon in human cells after TDP-43 knockdown. The claim is inaccurate in calling the human-cell experiment a knockout. (LLM, conf=0.90)
- Not matchedcites Saldi et al. 2018
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“blocking caspase-3-mediated cell death in these glia is sufficient to prevent glial loss but causes many more neurons to die”
What the sources say
- Supportedcites Chang & Dubnau 2019 source
In the Results subsection on glial toxicity to nearby neurons (Figure 6G–J), inhibiting Caspase-3 with p35 or DIAP-1 protected hTDP-43-expressing glia from dying. The same passage reports more Caspase-3-labeled nearby neurons and fewer surviving neurons at Day 4. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Elegant experiments have demonstrated that pathological TDP-43 can be transferred between cells in culture (Feiler et al. 2015, Shimonaka et al. 2016), leading to seeding and pathological mislocalization in recipient cells.”
What the sources say
- Partly supportedcites Feiler et al. 2015 sourceExperimental — accuracy not yet measured
The Results section on TDP-43 oligomerization in recipient cells reports that cell-culture-derived TDP-43 was taken up and triggered oligomerization; the Discussion also reports seeding activity and granule formation in target cells. Feiler et al. do not demonstrate pathological mislocalization of the recipient cells’ TDP-43. The Introduction attributes nuclear-to-cytoplasmic redistribution to Zhu et al. (2014). (LLM, conf=0.85)
- Not checked — no full text of the sourcecites Shimonaka et al. 2016 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Overexpression of human TDP-43 in glia or neurons causes (a) hyperphosphorylated cytoplasmic TDP-43 accumulation and (b) nuclear TDP-43 depletion”
What the sources say
- Partly supportedcites Chang & Dubnau 2019 sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says TDP-43 overexpression in animal models can cause cytoplasmic inclusions and loss of nuclear localization. It does not say those inclusions are hyperphosphorylated or establish both changes specifically in glia and neurons; the Results passages describe glial hTDP-43 toxicity and effects on nearby neurons instead. (LLM, conf=0.86)
- Supportedcites Krug et al. 2017 source
The Results section, “Neuronal and glial hTDP-43 expression causes age-dependent neurological deterioration” (page not provided), reports a disease-specific phosphorylated form of human TDP-43 together with cytoplasmic accumulation and nuclear clearance in the fly CNS. This supports the claim about the effects of neuronal or glial expression in the Drosophila model. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“There is no fully functional HERV-K in the human genome, but a number of HERV-K proviruses are capable of making one or several of the viral proteins”
What the sources say
- Supportedcites Contreras-Galindo et al. 2015 source
The IMPORTANCE passage states that no single endogenous retrovirus sequence identified in the human genome encodes a complete infectious virus, while different HERV-K (HK2) loci retain the capacity to encode functional viral proteins. This supports both parts of the paraphrase; no page number is supplied for the passage. (LLM, conf=0.93)
- Partly supportedcites Dewannieux et al. 2006 sourceExperimental — accuracy not yet measured
The Abstract says that no HERV-K provirus able to produce infectious particles had yet been described, and that several loci have complete viral-protein coding sequences. But it does not establish that no fully functional HERV-K exists in the human genome; the Discussion says some human alleles might still be functional. (LLM, conf=0.87)
- Partly supportedcites Hohn et al. 2013 sourceExperimental — accuracy not yet measured
The Introduction says many HERV-K(HML-2) proviruses retain open reading frames for functional viral proteins. The Postintegrational Mutations and Replication Potential section says no currently known HERV-K(HML-2) element appears able to produce infectious particles, but it does not rule out a rare infectious provirus. The claim makes that qualified finding categorical and extends it from HML-2 to all HERV-K. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The Drosophila genome harbors fully functional copies of mdg4, and there is direct evidence for intercellular viral transmission that requires the Env gene”
What the sources say
- Partly supportedcites Keegan et al. 2021 sourceExperimental — accuracy not yet measured
The Results (‘Intercellular transmission of gypsy requires Env’; page unavailable) directly show cell-free transmission of gypsy in cultured S2 cells and that deleting Env nearly abolishes it. The Discussion says intact gypsy copies in the Drosophila reference genome appear to contain an Env reading frame, but our copy does not identify them as mdg4 or establish that those genomic copies are fully functional. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“These features are in many ways similar to what has been described for cellular senescence in other neurodegenerative contexts”
What the sources say
- Not checked — no full text of the sourcecites Lee et al. 2023 source
- Supportedcites Musi et al. 2018 source
The Discussion describes senescence-like features in tau-associated neurodegeneration and says findings in human Alzheimer’s disease and progressive supranuclear palsy brain tissue support this connection. It also identifies features consistent with cellular senescence in the brain, supporting the broad comparison to other neurodegenerative contexts. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The individual glial cells marked by the mdg4-CLEVR reporter also exhibit DNA damage and activated caspase-3, as do nearby neurons”
What the sources say
- Partly supportedcites Chang & Dubnau 2019 sourceExperimental — accuracy not yet measured
The Results section on glial hTDP-43 pathology (Fig. 3D–L; page unavailable) reports DNA damage and activated Caspase-3 in glia positive for the gypsy-CLEVR reporter, with both markers also observed in some nearby neurons. The claim names an mdg4-CLEVR reporter instead; our copy identifies the reporter in these experiments as gypsy-CLEVR. (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Such transposition could be suppressed via caloric restriction or pharmacological blockage of reverse transcription.”
What the sources say
- Supportedcites Sun et al. 2018 source
The Results section reports that 66% dietary restriction reduced tau-induced transposable element mobilization in adult Drosophila neurons. It also reports reduced mobilization-reporter activation in tau transgenic flies treated with 3TC, a reverse-transcriptase inhibitor. These findings support the claim in the studied fly model. (LLM, conf=0.93)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Both interventions were found to reduce neurodegeneration, suggesting that the generation of new retrotransposon DNA copies is neurotoxic.”
What the sources say
- Supportedcites Sun et al. 2018 source
The Results section reports that both dietary restriction and the reverse-transcriptase inhibitor 3TC reduced tau-induced transposable-element mobilization and neuronal death in Drosophila. The Discussion describes transposable-element jumping as detrimental and interprets the interventions as evidence that dysregulation harms neuronal survival. This supports the claim as a suggested mechanism, not a proven exclusive cause. (LLM, conf=0.88)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Astrocytic dsRNA deposition is conserved in brains of tau transgenic mice and in patients with AD or PSP and occurs alongside elevation of the RIG-I-like dsRNA sensor MDA5 (Ochoa et al. 2023), consistent with previous reports of elevated RIG-I in the brains of patients with mild cognitive impairment (de Rivero Vaccari et al. 2014).”
What the sources say
- Supportedcites Ochoa et al. 2023 source
The Results sections report enriched astrocytic dsRNA in human tauopathy, including AD and PSP, and in rTg4510 tau transgenic mice. They also report elevated astrocytic MDA5 in both, identifying it as a member of the RIG-I-like receptor family. The cited source is not being used for the separate claim about RIG-I in mild cognitive impairment. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“When human Drosophila S2 cells expressing human TDP-43 are grown in the presence of cells expressing a fluorescently tagged mdg4-ERV, they can become infected with the tagged ERV, triggering the loss of nuclear TDP-43 and the accumulation of cytoplasmic phosphorylated TDP-43 in the recipient cells (Chang & Dubnau 2023).”
What the sources say
- Supportedcites Chang & Dubnau 2023 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“While these studies stand in slight contrast with an Aβ-based Drosophila model in which several retrotransposon transcripts were found to be elevated (Maggiore et al. 2022), it is clear that pathogenic forms of tau can drive the transcriptional elevation of retrotransposons independently of Aβ.”
What the sources say
- Supportedcites Maggiore et al. 2022 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Similarly, three different mouse models of tauopathy feature disease stage–dependent robust elevation of retrotransposon transcripts, while retrotransposons lack differential expression in a mouse model of Aβ pathology (Ramirez et al. 2022).”
What the sources say
- Partly supportedcites Ramirez et al. 2022 sourceExperimental — accuracy not yet measured
The Results section reports age-dependent elevation of retrotransposon transcripts across three mouse models of tauopathy. But it does not report a complete absence of differential expression in the APP/PS1 amyloid model: it detects three differentially expressed retrotransposons, two of them decreased. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Subsequent studies in brains of tau transgenic mice indicate that a tau-induced increase in LINE-1 and ERV1/ERVK DNA copy number is conserved in mammalian systems and is dependent upon disease stage (Ramirez et al. 2022).”
What the sources say
- Partly supportedcites Ramirez et al. 2022 sourceExperimental — accuracy not yet measured
The Results section ('Transposable element DNA copy number is elevated in tau transgenic mice'; page unavailable) reports increased L1, ERVK and ERV1 DNA copy number in tau transgenic mouse brains, particularly at 12 months. It concludes that the increase is age-dependent, but does not establish that DNA copy number depends on disease stage independently of age. (LLM, conf=0.84)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Cells exhibiting Gag elevation in brains of tau transgenic mice are not the cells that also harbor disease-associated phospho-tau, suggesting that Gag elevation is non–cell autonomous (Ramirez et al. 2022).”
What the sources say
- Supportedcites Ramirez et al. 2022 source
The Results section (“Increase in protein encoded by an active ERV in brains of tau transgenic mice”) states that cells with elevated IAP-gag in rTg4510 mouse brains are not the cells harboring AT8-positive, disease-associated phospho-tau. It explicitly says this suggests tau-induced ERV activation is non-cell autonomous. (LLM, conf=0.95)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“While the overexpression of Gag/Pol and ENV elevated tau propagation, spreading was found to be most efficient when active viral particles were produced by donor cells.”
What the sources say
- Supportedcites Liu et al. 2023 source
The Results section, “Retroviral proteins promote the spreading of NM and Tau aggregates” (Fig. 6k–p), reports increased Tau aggregate induction after donor transfection with retroviral plasmids and the highest induction when donors received gag/pol, env, and a transfer vector. The authors conclude that Env, Gag, and Pol promote spreading, but spreading is most efficient when donor cells produce active viral particles. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Similar findings have been reported in the context of physiological aging (Gulen et al. 2023) and other age-related neurodegenerative disorders ( Supplemental Table 1 ).”
What the sources say
- Supportedcites Gulen et al. 2023 source
The citing sentence attaches Gulen et al. (2023) to the physiological-ageing finding, not to the separate claim about other neurodegenerative disorders. In “cGAS–STING affects brain ageing” (page unavailable), the paper reports that inhibiting STING reduced microgliosis and protected against neuronal loss in aged mice, supporting a similar finding in natural ageing. (LLM, conf=0.91)
- Not matchedcites Supplemental Table 1
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“While it is currently unknown whether tau-induced retrotransposons form eccDNA, recent work from Gan's group (Udeochu et al. 2023) suggests that the cGAS-STING pathway is robustly activated in brains of tau transgenic mice, consistent with previous work in primary microglia treated with tau aggregates (Jin et al. 2021).”
What the sources say
- Supportedcites Udeochu et al. 2023 source
The Results section, “cGAS–STING is activated in tau transgenic mice and human AD,” reports increased TBK1 phosphorylation and microglial STING expression in P301S tau transgenic hippocampi relative to controls. The Discussion also describes strong cGAS activation in mice with tauopathy. The separate statement about earlier work in primary microglia is attributed to Jin et al., not to this source. (LLM, conf=0.94)
- Supportedcites Jin et al. 2021 source
The Jin et al. citation supports the comparison to tau-treated microglia, not the separate claim about Gan’s group and transgenic mouse brains. In Results (‘Tau activates cGAS–STING pathway in microglia’; page unavailable), polymerized tau induced NFκB nuclear translocation in microglia, although less efficiently than non-polymerized tau. The Results on PQBP1 confirm that tau-induced pathway activation was tested in primary microglia. (LLM, conf=0.86)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Subsequent reanalysis of the AMP-AD and ROSMAP data sets by other groups confirmed the initial findings of these studies (Grundman et al. 2021, Wahl et al. 2023).”
What the sources say
- Partly supportedcites Grundman et al. 2021 sourceExperimental — accuracy not yet measured
The Methods say Grundman et al. reanalyzed RNA-sequencing data from the AMP-AD Knowledge Portal, and the Discussion says their TE-expression analysis largely confirmed earlier findings of ERV activation. The cited paper does not identify a ROSMAP reanalysis, so it supports the AMP-AD portion of the claim but not the claim about both datasets. (LLM, conf=0.85)
- Supportedcites Wahl et al. 2023 source
The Experimental Procedures (Human brain transcriptome analyses; page unavailable) say the authors analyzed existing ROSMAP RNA-seq data. The Results (TE transcripts increase in human brain aging; page unavailable) report increased transposable-element transcripts in Alzheimer’s disease cases and say the results are consistent with previous reports. Wahl et al. thus support the ROSMAP reanalysis portion of the jointly cited claim; this paper does not analyze AMP-AD. (LLM, conf=0.87)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Neuronal overexpression of Dicer-2, a dsRNA clearance factor in Drosophila, suppresses tau-induced dsRNA accumulation (Ochoa et al. 2023), supporting a model in which tau-induced retrotransposon dsRNAs are produced and secreted from neurons and are taken up by astrocytes.”
What the sources say
- Supportedcites Ochoa et al. 2023 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Astrocytic dsRNA deposition is conserved in brains of tau transgenic mice and in patients with AD or PSP and occurs alongside elevation of the RIG-I-like dsRNA sensor MDA5 (Ochoa et al. 2023), consistent with previous reports of elevated RIG-I in the brains of patients with mild cognitive impairment (de Rivero Vaccari et al. 2014).”
What the sources say
- Supportedcites de Rivero Vaccari et al. 2014 source
The Results section ('RIG-1 is elevated in the temporal cortex of MCI patients') reports increased RIG-1 expression in temporal cortical samples from patients with mild cognitive impairment compared with controls and patients with AD. The studied MCI patients had pathology consistent with possible or probable AD. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The lamin nucleoskeleton becomes destabilized in neurons of transgenic Drosophila expressing pathogenic forms of tau, in tau transgenic mice, in human brains from patients with AD or FTD due to MAPT mutation, in induced pluripotent stem cell–derived neurons carrying MAPT mutations, and in cells with induced tau expression or aggregation (Fernández-Nogales et al. 2017, Frost et al. 2016, Jiang et a”
What the sources say
- Not matchedcites Fernández-Nogales et al. 2017
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Frost et al. 2016
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites Jiang et al. 2021 sourceExperimental — accuracy not yet measured
The Results section, “Tau oligomerization elicits disruption of the nuclear envelope” (page unavailable), reports LaminB2 redistribution and insolubility in neurons with induced tau oligomerization, as well as nuclear-envelope disruption in P301S tau mice. It does not establish the claimed lamin destabilization in Drosophila, human AD or MAPT-related FTD brains, or MAPT-mutant induced pluripotent stem cell–derived neurons. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
Every source the paper cites for this claim was checked and supports it.
In the paper
“Similarly, NRTIs reduce the toxicity of transgenic TDP-43 overexpression (Krug et al. 2017) or knockout of the endogenous fly ortholog (Romano et al. 2020).”
What the sources say
- Supportedcites Krug et al. 2017 source
Krug et al. report in the Results section (‘RTE and Chk2 activity mediate effects of hTDP-43 on lifespan and cell death’; page unavailable) a mild but significant lifespan extension after pharmacological inhibition of reverse transcriptase in flies expressing transgenic hTDP-43. The Methods section identifies the treatments as NRTIs. The knockout claim is attributed to Romano et al., not to Krug et al. (LLM, conf=0.90)
- Supportedcites Romano et al. 2020 source
The Results section reports that NRTI treatment reversed locomotor defects in TBPH-null fly larvae; the Fig. 2 caption separately identifies the NRTI-treated group. Romano et al. supports the knockout portion of the citing sentence. The transgenic TDP-43 overexpression portion is attributed to Krug et al., not Romano et al. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“piRNA biogenesis pathways have not been established in the brain, and piRNA-like sequences in the brain have not yet been shown to load onto Piwi protein”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“There is a large body of work implicating retrotransposon activation in the pathophysiology of human aging and myriad human disorders, including adult-onset age-related neurodegenerative conditions”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“a subset of these elements, the endogenous retroviruses (ERVs), also encode an envelope glycoprotein that mediates intercellular spread”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“TDP-43 pathology is a defining feature of most (but not all) ALS cases and is prevalent in many cases of FTD and AD”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“many of these elements can still be transcribed, form double-stranded RNAs (dsRNAs) due to bidirectional transcription or backfolding of inverted repeats, encode viral-like proteins, exist as extrachromosomal circular DNA (eccDNA), and cause DNA damage”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“GRN, C9orf72, or TDP-43 mutations exhibit TDP-43 proteinopathy”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite some variation among ALS or FTD subtypes, each of these studies report broad retrotransposon activation in ALS/FTD, and two out of three found a correlation with TDP-43 pathology burden.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Among the 30% of FTD cases that are genetic, most are due to mutations in MAPT or GRN or repeat expansions in C9orf72.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“patients with frontotemporal dementia (FTD) often also exhibit motor neuron involvement matching the diagnostic criteria of amyotrophic lateral sclerosis (ALS)”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“This finding is broadly consistent with a connection between TDP-43 pathology and retrotransposon activation because such proteinopathy is commonly observed in C9orf72 familial ALS”
What the sources say
- Not checked — no full text of the sourcecites Al-Sarraj et al. 2011 source
- Not matchedcites Saberi et al. 2018
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“this may have been due to methodological challenges associated with polymerase chain reaction from repetitive sequences and/or from significant variation in the postmortem interval and RNA integrity values”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“It also found evidence for direct binding of TDP-43 to retrotransposon RNAs in RNA immunoprecipitation (RIP)-seq and cross-linking immunoprecipitation (CLIP)-seq data sets.”
What the sources say
- Not matchedcites Li et al. 2012
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
- Not matched
In the paper
“In Drosophila, for example, neuronal or glial human TDP-43 overexpression broadly elevates retrotransposon transcripts (Li et al. 2013), with some key differences in which retrotransposons are impacted from neuronal versus glial TDP-43 expression.”
What the sources say
- Not matchedcites Li et al. 2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It seems likely that the loss of nuclear TDP-43 function drives retrotransposon activation, as knockout or knockdown of TDP-43 or its orthologs activates retrotransposons in Caenorhabditis elegans, Drosophila, and cultured human cells.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“If the right combination of HERV-K elements was transcribed, all viral proteins could in principle be produced.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Combined with studies in postmortem tissues, these findings from flies, worms, and human cells support the hypothesis that TDP-43 is a core component of the retrotransposon silencing machinery in the nervous system and that the loss of nuclear TDP-43 function yields broad increases in retrotransposon expression.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, in addition to the fact that TDP-43 pathology triggers retrotransposon expression, expression of ERVs can also stimulate TDP-43 pathology, providing the potential for a feedback amplification mechanism.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Transgenic mice with pan-neuronal HERV-K ENV expression exhibit progressive motor dysfunction, loss of neuronal volume in motor cortex, muscle atrophy, and degenerative effects in the anterior horn of the spinal cord.”
What the sources say
- Not matchedcites Li et al. 2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that tau-induced retrotransposon activation generates cDNA that could (a) integrate into genomic DNA, causing a novel somatic insertion; (b) attempt to integrate into genomic DNA and fail, causing DNA double-strand breaks; and/or (c) exist as eccDNA that drives innate immune activation.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Reverse transcription of retrotransposon RNA produces new DNA copies.
In the paper
“Genetic manipulation of Arc1 was found to modify tau neurotoxicity in Drosophila, suggesting that tau-induced Arc1 elevation is a causal factor driving neurodegeneration (Schulz et al. 2023).”
What the sources say
- Not matchedcites Schulz et al. 2023
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“ARC protein levels are elevated in postmortem human brain tissue from patients with AD (Wu et al. 2011), and Drosophila Arc1 transcripts (Zuniga et al. 2023) and Arc1 protein multimers (Schulz et al. 2023) are elevated in brains of tau transgenic Drosophila, suggestive of capsid formation.”
What the sources say
- Not matchedcites Zuniga et al. 2023
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites Schulz et al. 2023
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, these studies suggest that these elements may exist as eccDNA that could activate an antiviral cGAS-STING response.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Rests on an assumption: Compared to the Drosophila and mouse genomes, the human genome possesses significantly fewer retrotransposons that are transpositionally competent.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“These experiments do not distinguish whether pathological TDP43 is transferred along with viral particles, or whether the movement of viral particles is sufficient to reinitiate pathological transformation of TDP-43 within recipient cells.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is important to note that reverse transcriptase inhibitors would, in theory, reduce TE insertions, DNA double-strand breaks, and potentially neuroinflammatory eccDNA.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Rests on an assumption: Reverse transcription of retrotransposon RNA produces new DNA copies.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“3TC nevertheless clearly suppresses tau and TDP-43 neurotoxicity in invertebrate models and tau toxicity in vertebrate models.”
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Multiple clinical trials utilizing antiretroviral therapy for AD, primary tauopathies, and TDP-43 pathologies are ongoing ( Table 1 ).”
What the sources say
- Not matchedcites Table 1
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As noted above, reverse transcriptase inhibitors would block the production of DNA that can insert into the genome, generate DNA double-strand breaks, or exist as inflammatory eccDNA.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
- Rests on an assumption: Reverse transcription of retrotransposon RNA produces new DNA copies.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Although there is evidence from animal models for causal impacts, it remains to be seen whether retrotransposon activity affects relevant clinical outcomes.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Astrocytes express scavenger receptors that recognize dsRNAs in the extracellular milieu and facilitate their uptake and degradation and can also respond to viral infection by producing dsRNA endogenously (Salmina et al. 2015).”
What the sources say
- Not checked — no full text of the sourcecites Salmina et al. 2015 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Over 40% of the human genome is composed of retrotransposons.
“Over 40% of the human genome is composed of retrotransposons”
“Based on the fact that they occupy 40% of the human genome”
The authors state this as an assumption.
Mechanisms underlying the onset and progression of neurodegeneration are shared primarily based on the type of protein pathologies observed rather than clinical presentation.
“Based on the overlapping protein pathology across disorders and heterogeneity within disorders, we conjecture that mechanisms underlying the onset and progression of neurodegeneration are shared primarily based on the type of protein pathologies observed rather than clinical presentation.”
The paper relies on this without support.
Findings from Drosophila and mouse models of TDP-43 pathology can be generalized to human TDP-43 proteinopathies.
“Work in animal models also provides some mechanistic insight and evidence for a causal impact of retrotransposons on neurodegeneration.”
“These features are in many ways similar to what has been described for cellular senescence in other neurodegenerative contexts”
The authors state this as an assumption.
Retrotransposon cDNA synthesis is a critical step along the pathway to neurodegeneration.
“This approach makes the assumption that retrotransposon cDNA synthesis is a critical step along the pathway to neurodegeneration.”
The paper relies on this without support.
Pathological TDP-43 seeds conformational changes through a prion-like mechanism.
“Pathological TDP-43 seeds conformational changes through a prion-like mechanism, and intercellular movement of pathological TDP-43 is proposed to explain the propagation of degenerative effects between cells.”
The paper relies on this without support.
Compared to the Drosophila and mouse genomes, the human genome possesses significantly fewer retrotransposons that are transpositionally competent.
“Compared to the Drosophila and mouse genomes, the human genome possesses significantly fewer retrotransposons that are transpositionally competent.”
The paper relies on this without support.
Reverse transcription of retrotransposon RNA produces new DNA copies.
“Reverse transcription of retrotransposon RNA produces new DNA copies.”
Citations
Cites
Initial sequencing and analysis of the human genome
International Human Genome Sequencing Consortium, Whitehead Institute for Biomedical Research, C. F. G. R., Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., Devon, K., Dewar, K., et al. (2001) · Nature · doi:10.1038/35057062 · Cited by 24,216
Inflammaging: a new immune–metabolic viewpoint for age-related diseases
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Self-citation
Metadata
- Authors
- Frost, B., & Dubnau, J.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Stony Brook School (US)
- Venue
- Annual Review of Neuroscience
- Publisher
- Annual Reviews
- Published
- 2024-08-08
- Volume
- 47
- Issue
- 1
- Pages
- 123-143
- ISSN
- 0147-006X (ISSN-L)
- 1545-4126
- OpenAlex
- W4395448296
- Semantic Scholar
- 084e8e08c8d127cd2e28747ef4aba97612974519
- Cited by
- 45
- References
- 135
- Citations by year
- 2026: 22 · 2025: 20 · 2024: 3
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Annual Review of Neuroscience (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG078788, RF1AG076493)
- National Institute of Neurological Disorders and Stroke (RF1 NS112391)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- retrotransposons, endogenous retroviruses, age-related neurodegenerative disorders, TDP-43, tau protein, retrotransposon activation, innate immune activation, neurotoxicity, extrachromosomal circular DNA, double-stranded RNA, insertional mutagenesis, clinical trials
- MeSH terms
- Aging, Animals, DNA-Binding Proteins, Humans, tau Proteins, Retroelements, Neurodegenerative Diseases, Endogenous Retroviruses
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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Statistics and arithmetic are recomputed, not judged.
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