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
- 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
Franceschi, C., Garagnani, P., Parini, P., Giuliani, C., & Santoro, A. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0059-4 · Cited by 3,586
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498
Discrete Small RNA-Generating Loci as Master Regulators of Transposon Activity in Drosophila
Brennecke, J., Aravin, A. A., Stark, A., Dus, M., Kellis, M., Sachidanandam, R., & Hannon, G. J. (2007) · Cell · doi:10.1016/j.cell.2007.01.043 · Cited by 2,524
An integrated map of structural variation in 2,504 human genomes
Sudmant, P. H., Rausch, T., Gardner, E. J., Handsaker, R. E., Abyzov, A., Huddleston, J., Zhang, Y., Ye, K., Jun, G., Hsi-Yang Fritz, M., et al. (2015) · Nature · doi:10.1038/nature15394 · Cited by 2,354
Transposable elements and the epigenetic regulation of the genome
Slotkin, R. K., & Martienssen, R. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2072 · Cited by 2,044
The origin and behavior of mutable loci in maize
McClintock, B. (1950) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.36.6.344 · Cited by 1,752
Tau is a candidate gene for chromosome 17 frontotemporal dementia
Poorkaj, P., Bird, T. D., Wijsman, E., Nemens, E., Garruto, R. M., Anderson, L., Andreadis, A., Wiederholt, W. C., Raskind, M., & Schellenberg, G. D. (1998) · Annals of Neurology · doi:10.1002/ana.410430617 · Cited by 1,374
Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline
Bussian, T. J., Aziz, A., Meyer, C. F., Swenson, B. L., van Deursen, J. M., & Baker, D. J. (2018) · Nature · doi:10.1038/s41586-018-0543-y · Cited by 1,289
L1 drives IFN in senescent cells and promotes age-associated inflammation
De Cecco, M., Ito, T., Petrashen, A. P., Elias, A. E., Skvir, N. J., Criscione, S. W., Caligiana, A., Brocculi, G., Adney, E. M., Boeke, J. D., et al. (2019) · Nature · doi:10.1038/s41586-018-0784-9 · Cited by 1,255
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Sorted by citations
Kozubek, P., Kuźniar, J., Czaja, M., Sitka, H., Kochman, U., & Leszek, J. (2024) · Biomedicines · doi:10.3390/biomedicines13010059 · Cited by 11
Funaguma, S., Iida, A., Saito, Y., Tanboon, J., Reyes, F. V. D. L., Sonehara, K., Goto, Y., Okada, Y., Hayashi, S., & Nishino, I. (2025) · Nature Communications · doi:10.1038/s41467-025-56567-6 · Cited by 14
“…sarcoidosis We also analyzed the genetic association between THE1B fusion tran-scriptsandPRRsinscRNA-seqdataobtainedandintegratedfromthree individuals with cutaneous sarcoidosis, employing Pearson ’ s correlation coef fi cient to assess the strength of these associations (Supplementary Data 6).”
InfluentialTE-Seq: a transposable element annotation and RNA-Seq pipeline
Kelsey, M. M. G., Kalekar, R. L., & Sedivy, J. M. (2025) · Mobile DNA · doi:10.1186/s13100-025-00381-w · Cited by 11
“Their less welcome participation in patho-physiological processes is also well documented, wherein they have been shown to promote chronic inflammation, tumorigenesis, and neurodegeneration [3–5].”
Human Endogenous Retroviruses and Diseases
Chen, C., Cui, Y., Wang, S., Yang, Y., Liu, Z., Jin, S., Shen, F., Gaipl, U. S., Ma, H., & Zhou, J. (2025) · MedComm · doi:10.1002/mco2.70452 · Cited by 10
“Intrinsic mechanisms involve epigenetic reprogramming: dynamic histone modifications (e.g., NF-κ B-dependent in inflammation) and DNA methylation changes [109, 110].”
Ramirez, P., Sun, W., Dehkordi, S. K., Zare, H., Pascarella, G., Carninci, P., Fongang, B., Bieniek, K. F., & Frost, B. E. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70852 · Cited by 9
Self-citationMangoni, D., Mazzetti, A., Ansaloni, F., Simi, A., Tartaglia, G. G., Pandolfini, L., Gustincich, S., & Sanges, R. (2024) · BioEssays · doi:10.1002/bies.202400125 · Cited by 9
Virus-like particles of retroviral origin in protein aggregation and neurodegenerative diseases
Carra, S., Fábián, B., Taghavi, H. V., Milanetti, E., Giliberti, V., Ruocco, G., Shepherd, J. D., Vendruscolo, M., & Fuxreiter, M. (2025) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2025.101369 · Cited by 7
“VLP-forming proteins are associated with a wide range of neurological disorders (Frost and Dubnau, 2024; Ochoa Thomas et al., 2020; Payer and Burns, 2019; Jonsson et al., 2020; Pandya et al., 2021).”
Insights into the therapeutic strategies for aging and aging-associated diseases
Dong, R., Wu, Q., Kan, J., Fu, C., Sorrentino, V., Chow, A., Lei, Y., Wu, D., Xu, Z., Du, J., et al. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02662-z · Cited by 12
“250,251 Liu ’ s group systematically de fi ned and revealed that aging-induced resurrection of endogenous retro-virus can serve as a hallmark of senescence.”
Wu, Y. X., Huang, S., Sha, Q., & Yu, J. (2025) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2025.101422 · Cited by 8
Role of LINE-1 in the nervous system and neurological disorders
Hu, H., Lu, X., Zhong, R., Liu, X., Wei, J., Duan, C., & Sun, N. (2025) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003891 · Cited by 5
“[66] In FTLD patients with mutations in the TDP-43 gene, this binding was significantly reduced, resulting in increased transcription of LINE-1 retrotransposons.”
Endogenous retroviruses in neurodevelopmental, psychotic and cognitive disorders
Meyer, U., & Penner, I. (2025) · Microbes and Infection · doi:10.1016/j.micinf.2025.105479 · Cited by 5
Li, T. D., Toohill, K., & Modzelewski, A. J. (2025) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.70022 · Cited by 5
Dormant viral pathways underlie space-induced neural senescencePreprint
Martins, A. M. A., Nakashima, H., Macia, Á., Umeyama, T., Miyashita, S., Nascimento, L. L., Coelho, L. B. V., Mesci, P., Viirre, E., Suarez, N., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.02.686043 · Cited by 6
Retrotransposons unplugged: Rewiring the nervous system and wreaking havoc
Whiteley, A. M., & Shepherd, J. D. (2025) · Neuron · doi:10.1016/j.neuron.2025.09.034 · Cited by 4
Impact of Transposable Elements on DNA Double-Strand Break Repair and Genomic Stability
Bhat, M. I., PANDITA, R. K., Mushtaq, A., Mir, U. S., Saqib, N., Sarkar, P. S., Bhat, A., Ramos, K. S., Pandita, T. K., & Altaf, M. (2026) · Molecular and Cellular Biology · doi:10.1080/10985549.2025.2594182 · Cited by 2
“152 Recent functional genomics studies have identified TE mobilization in heterochromatic regions as a major genomic shift in Alzheimer ’ s disease (AD).”
RNA transcripts in salivary extracellular vesicle cargo isolated from aged populations
Wen, S., Chang, Y., Kelsey, M. M. G., Pereira, M., Alaimo, H., Teixeira, E. M., Pracht, J. R., Daiello, L. A., Drake, J. D., Sedivy, J. M., et al. (2026) · Frontiers in Aging · doi:10.3389/fragi.2025.1707720 · Cited by 2
The role of retrotransposons at the interface of DNA damage and the innate immune response
Vikraman, P., Davoli, T., & Mita, P. (2026) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2026.102625 · Cited by 2
Single-Cell Transcriptome Patterns of Transposable Elements in Alzheimer’s Disease
McEntee, C. M., & LaRocca, T. J. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05140-9 · Cited by 4
“We and others have shown that TE transcripts (including active and potentially deleterious LINEs and LTRs) increase with AD and other neurodegenerative diseases in the brain [9–13, 48, 49], as well as in normal aging and age-related diseases in other tissues [7, 8, 42, 50, 51].”
Aging and human endogenous retroviruses
Xu, C., Zhu, F., & Cui, J. (2025) · hLife · doi:10.1016/j.hlife.2025.07.002 · Cited by 2
Identification of novel regulators of LINE-1 expression via CRISPR/Cas9 screening
Oksuz, O., Chu, C., Arisdakessian, C. G., Diao, L., Zaller, D. M., Long, K. K., Keilhack, H., & Knutson, S. K. (2025) · Mobile DNA · doi:10.1186/s13100-025-00386-5 · Cited by 1
Longitudinal Repeatome Remodeling in Peripheral Blood Following Parkinson’s Disease Diagnosis
Kulski, J. K., & Kõks, S. (2026) · Genes · doi:10.3390/genes17050577 · Cited by 1
“In contrast, ERV subfamilies represented a substantial proportion of the overlapping PD-associated repeat signatures, consistent with growing evidence that ERV-associated transcription may contribute to immune-responsive molecular states in neurodegenerative disease [66,67].”
Oriquat, G., Abdulqader, A. F., Farid, H., Ashurov, Z., Sottarov, A., Ghafl, N. Y., Bainsal, N., & Singh, R. (2026) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2026.111963 · Cited by 3
Dayama, G., Gupta, S., Connizzo, B. K., Labadorf, A. T., Myers, R. H., & Lau, N. C. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.22.619758
Neural development goes retro: Gags as essential modulators of synapse formation
Chang, Y., & Dubnau, J. (2025) · PLoS Biology · doi:10.1371/journal.pbio.3003032
“There is accumulating evidence that when these silencing systems fail, RTEs contribute to diseases such as cancer and neurodegeneration, as well as to the normal aging process [4,5].”
Self-citationLicastro, F. (2025) · Biocell · doi:10.32604/biocell.2025.062303
“It has been suggested that the tau-induced retrotransposon activation also generates cDNA that integrates into genomic DNA, causing a novel somatic insertion [27].”
InfluentialcircSATB1 Modulates Cell Senescence in Age-Related Acute Myeloid Leukemia: A Mechanistic Proposal
Han, L., Wen, X., Zhang, L., Yang, X., Wei, Z., Wu, H., Zhan, Y., Wang, H., & Yu, F. (2025) · Cells · doi:10.3390/cells14151181
“CircRNA, a class of highly stable non-coding RNA with multidimensional regulatory functions, exhibits complex regulatory networks in the pathogenesis of age-related diseases and the aging process [10].”
M'angale, P. G., Oliver, D., Alegre, G., Graslie, J., Tran, A., Ohira, A., Zinter, M., Malinkevich, A., & Thomson, T. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.17.676627
Ávila, J., Hernández, F., & Viña, J. (2025) · Geromedicine · doi:10.70401/geromedicine.2025.0006
Retrotransposons as both “architects” and “saboteurs” in the nervous system
Izquierdo‐Useros, N., Dierssen, M., Clotet, B., Elizalde‐Torrent, A., & Carriba, P. (2025) · Advances in genetics · doi:10.1016/bs.adgen.2025.11.002 · Cited by 2
Logotheti, S., Yildiz, E., Hasan, S., Theodoridou, E., Kuhn, S., Stiewe, T., Marquardt, S., Pavlopoulou, A., & Seco, J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.06.704391
“…ERVs turns beneficial for the host, especially for promoting abscopal effects, need thorough characterization, since ERVs could also act as double-edged swords favoring autoimmunity 42 , aging 52 , neurodegenerative disorders 53 or (upon chronic expression) evolution of tumour immune evasion 54 .”
Implications of virus-induced stress granules in tauopathies
Sharma, S., Vandenakker, A., Cortes-Pérez, C. M., Milne, S., & Douville, R. N. (2026) · Translational Neurodegeneration · doi:10.1186/s40035-026-00538-4
“Moreover, TE-encoded proteins play roles in neurode-generation (recently reviewed in [157, 158]).”
InfluentialTYK2 mediates neuroinflammation in Alzheimer’s disease brains with TDP-43 pathology
König, L. E., Rodriguez, S., Hug, C. B., Daneshvari, S., Chung, A., Appleman, M., Tsai, M., Bradshaw, G. A., Şahin, A., Song, Y., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-70243-3 · Cited by 7
“Together, “ neuronin fl ammation ” , an emerging concept which includes endogenous accumulation of cdsRNA from genomic 80,81 , mitochondrial 82 , and viral 83 sources as well as other DAMPs 34 , likely interacts with astrocytic 84 and microglial 85 cascades to drive disease progression.”
Commentary: RNA transcripts in salivary extracellular vesicle cargo isolated from aged populations
Yin, L. (2026) · Frontiers in Aging · doi:10.3389/fragi.2026.1799802
“Frost and Dubnau comprehensively reviewed the role of retrotransposons and endogenous retroviruses, highlighting their activation as a contributing factor in age-related disorders involving TDP-43 and tau pathologies (Frost et al., 2024).”
Chen, Z., Liu, Y., Wang, H., Liu, K., Li, Y., Hu, X., Li, R., & Sun, L. (2026) · Alzheimer s Research & Therapy · doi:10.1186/s13195-026-02048-x
“At the same time, as discussed above, the aberrant changes in the included miRNAs may also be related to abnormal activation of transposable elements (TEs), which commonly accompanies neurodegenerative pathology [171].”
Abuhassan, Q., Saeed, T. N., Al-Hussainy, A. F., Roopashree, R., Mishra, S., Nanda, A., Mukherjee, G., Rizaev, J., Taher, S. G., Alwan, M., et al. (2026) · Journal of Molecular Neuroscience · doi:10.1007/s12031-026-02532-x · Cited by 1
“However, in aging and AD, the epigenetic barriers maintaining this suppression erode, leading to the resurrection of these viral mimicry drivers (Cardelli 2018; Frost and Dubnau 2024; Peze-Heidsieck et al. 2022).”
ERVK activity in CD8+ T cell immune cell compartment in patients with ALS
Sharma, S., Cortes-Pérez, C. M., Bird, S., Curzio, D. D., Vandenakker, A., Schellenberg, K. L., & Douville, R. N. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03871-7 · Cited by 1
“Given that viral mechanisms that may drive neuropathology in these cases (reviewed in [27, 72]), there has been keen interest in the possible use of antivirals to treat ALS and FTD [73, 74].”
The retroelement-derived human protein PEG10 is a regulator of mRNA splicing in neuronsPreprint
Matthews, A. M., & Whiteley, A. M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.21.727000 · Cited by 1
Dayama, G., Lee, J.-H. R., Gupta, S., Brion, C., Connizzo, B. K., Labadorf, A. T., Myers, R. H., & Lau, N. C. (2026) · Genome Research · doi:10.1101/gr.280565.125
Diagnosis and management of frontotemporal dementia: a narrative review.
Cenacchi, V., Lombardo, T., Palacino, F., Cattaruzza, T., Manganotti, P., & Benussi, A. (2026) · Neurodegenerative Disease Management · doi:10.1080/17582024.2026.2687481
Virus-mediated tau aggregate seeding in a cellular modelPreprint
Yuste‐Checa, P., Martinez-Piera, R. D., Herrmann-Sim, F., Ronquillo-Silva, L. S., Körner, R., & Hartl, F. U. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.25.734433
HUSH, NEXT PROMPT: Epigenetics and the Nuclear RNA Exosome in Human Aging and Disease
Newman, A. G., & Singh, P. B. (2026) · Cells · doi:10.3390/cells15151378
“These converging lines of evidence establish TE de-repression as a unifying mechanism across neurodegenerative diseases [191].”
Takahashi, F., Yamamura, T., & Oki, S. (2026) · iScience · doi:10.1016/j.isci.2026.117335
“22 9 Therefore, we examined whether CCR and L1 retrotransposition are involved in neurodegeneration.”
Millan, M. J. (2026) · Neuroscience Applied · doi:10.1016/j.nsa.2026.107024
“Underpinning this contention, several facets of cerebral dysfunction in SAND mimic those observed in brains of the elderly and in subjects afflicted with NDAs like AD and PD, conjuring up the spectre of mutual aggravation (Table 3) (Lee et al., 2024a; Sun et al., 2024; Popa et al., 2025; Casoli, 2022).”
InfluentialFlipons, Noncoding Transcripts and Retroelements: A Universal Host Defense
Herbert, A. G. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27198526
Murthygowda, S., Huyghue, K., Castillo, B., Gugala, F., Li, W., & Dubnau, J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.23.753732
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
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