The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index; 37 of the 52 sources its claims cite were checked for support.
Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies
Open accessAbstract
Transposable elements, known colloquially as 'jumping genes', constitute approximately 45% of the human genome. Cells utilize epigenetic defenses to limit transposable element jumping, including formation of silencing heterochromatin and generation of piwi-interacting RNAs (piRNAs), small RNAs that facilitate clearance of transposable element transcripts. Here we utilize Drosophila melanogaster and postmortem human brain samples to identify transposable element dysregulation as a key mediator of neuronal death in tauopathies, a group of neurodegenerative disorders that are pathologically characterized by deposits of tau protein in the brain. Mechanistically, we find that heterochromatin decondensation and reduction of piwi and piRNAs drive transposable element dysregulation in tauopathy. We further report a significant increase in transcripts of the endogenous retrovirus class of transposable elements in human Alzheimer's disease and progressive supranuclear palsy, suggesting that transposable element dysregulation is conserved in human tauopathy. Taken together, our data identify heterochromatin decondensation, piwi and piRNA depletion and consequent transposable element dysregulation as a pharmacologically targetable, mechanistic driver of neurodegeneration in tauopathy.
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61 Own result · 24 Own interpretation · 12 Supported · 12 Partly supported · 9 Own method · 8 No full text of the sources · 2 Supported so far · 1 Couldn’t confirm · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“We have previously identified tau-induced decondensation of constitutive heterochromatin as a key event that mediates neuronal death in tauopathy10.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > Abstract
What the sources say
- Supportedcites [10] Frost, B., Hemberg, M., Lewis, J. & Feany, M. B. Tau promotes neurodegeneration through global chromatin relaxation. Nat. Neurosci. 17, 357–366 (2014). source
The Results section, “Genetic manipulation of chromatin structure modifies tau neurotoxicity” (page not supplied), reports that restoring heterochromatin in tau-transgenic flies suppressed neuronal apoptosis and directly implicates heterochromatin loss in neuronal death. The paper also identifies the affected heterochromatin markers H3K9me2 and HP1α as enriched in constitutive heterochromatin. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Studies in Drosophila indicate that cell cycle activation is causal for neuronal death in tauopathy, and that activation of the cell cycle in neurons is sufficient to induce neuronal death18.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Loss of transposable element silencing mediates tau-induced neurotoxicity in Drosophila.
What the sources say
- Supportedcites [18] Khurana, V. et al. TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model. Curr. Biol. 16, 230–241 (2006). source
The Results section states that interfering with cell-cycle progression substantially reduces tau-induced neurodegeneration. It also reports that ectopic cell-cycle activation leads to apoptosis of postmitotic neurons in vivo, supporting the sufficiency claim in this Drosophila model. Page numbers are not provided in our copy. (LLM, conf=0.94)
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Multiple previous studies report that expression of human wild-type or R406W mutant tau involve the same major mechanisms of tau-induced neurotoxicity in Drosophila models10,16,20.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Drosophila models of human tauopathy have altered levels of transposable element transcripts
What the sources say
- Partly supportedcites [10] Frost, B., Hemberg, M., Lewis, J. & Feany, M. B. Tau promotes neurodegeneration through global chromatin relaxation. Nat. Neurosci. 17, 357–366 (2014). sourceExperimental — accuracy not yet measured
The Results section on chromatin structure reports that both wild-type and R406W tau reduce H3K9me2 and HP1α in Drosophila, supporting a shared heterochromatin-loss mechanism. The paper does not establish that the two forms involve the same major mechanisms of neurotoxicity more broadly; most subsequent mechanistic experiments use R406W tau. No page number is available in our copy. (LLM, conf=0.82)
- Partly supportedcites [16] Frost, B., Bardai, F. H. & Feany, M. B. Lamin dysfunction mediates neurodegeneration in tauopathies. Curr. Biol. 26, 129–136 (2016). sourceExperimental — accuracy not yet measured
The Results (page not provided) show that both wild-type and R406W tau reduce Lamin levels and cause Lamin invagination in Drosophila, supporting a shared pathway of toxicity. The paper does not establish that the two forms involve the same major mechanisms overall; its subsequent mechanistic experiments use R406W tau. (LLM, conf=0.84)
- Supportedcites [20] Bardai, F. H. et al. A conserved cytoskeletal signaling cascade mediates neurotoxicity of FTDP-17 tau mutations in vivo. J. Neurosci. 38, 108–119 (2018). source
The Discussion (page unavailable) explicitly says wild-type and R406W human tau activate common downstream mechanisms of toxicity in Drosophila. It also reports that both stabilize F-actin, a mechanism linked to neurotoxicity, although the magnitude differs between them. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Tau-induced heterochromatin relaxation plays a causal role in mediating neurodegeneration, as loss of function mutations in Su(var)20533 and Su(var)3-934, genes encoding heterochromatin protein 1 (HP1) and a histone 3, lysine 9 methyltransferase, respectively, further deplete constitutive heterochromatin in tau transgenic Drosophila and enhance tau-induced neuronal death10.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Decondensation of heterochromatin contributes to aberrant transposable element transcription in the adult Drosophila brain
What the sources say
- Supportedcites [10] Frost, B., Hemberg, M., Lewis, J. & Feany, M. B. Tau promotes neurodegeneration through global chromatin relaxation. Nat. Neurosci. 17, 357–366 (2014). source
The Results section (“Genetic manipulation of chromatin structure modifies tau neurotoxicity”) reports that Su(var)3-9 or Su(var)205 loss-of-function mutations exacerbated heterochromatin loss in tau transgenic flies and doubled neuronal apoptosis relative to tau expression alone. The authors explicitly conclude that heterochromatin loss plays a causal role in tau-induced neurotoxicity in vivo. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Studies in Drosophila indicate that cell cycle activation is causal for neuronal death in tauopathy, and that activation of the cell cycle in neurons is sufficient to induce neuronal death18.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Loss of transposable element silencing mediates tau-induced neurotoxicity in Drosophila.
What the sources say
- Supportedcites [18] Khurana, V. et al. TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model. Curr. Biol. 16, 230–241 (2006). source
The Introduction states that inhibiting cell-cycle transitions blocks neuronal apoptosis in the Drosophila tauopathy model, establishing a causal relationship. The Results also report reduced neurodegeneration when cell-cycle progression was inhibited. Page numbers are not provided in our copy's passages. (LLM, conf=0.95)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“We have previously reported widespread relaxation of constitutive heterochromatin, a form of hyper-condensed DNA, in postmortem brains from patients with Alzheimer’s disease, which is the most common tauopathy, and in Drosophila and mouse models of tauopathy10.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Decondensation of heterochromatin contributes to aberrant transposable element transcription in the adult Drosophila brain
What the sources say
- Supportedcites [10] Frost, B., Hemberg, M., Lewis, J. & Feany, M. B. Tau promotes neurodegeneration through global chromatin relaxation. Nat. Neurosci. 17, 357–366 (2014). source
The Results section, “Heterochromatin loss in vertebrate tauopathies,” reports heterochromatin loss in Drosophila and mouse tauopathy models and diffuse heterochromatin-marker staining in postmortem Alzheimer’s disease neurons. This supports the claimed finding across all three settings. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A causal association between HERV-K and neuronal dysfunction has previously been established, as ectopic expression of HERV-K or the retroviral envelope protein that it encodes decreases synaptic activity and induces progressive motor dysfunction in mice8”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > DISCUSSION
What the sources say
- Partly supportedcites [8] Li, W. et al. Human endogenous retrovirus-K contributes to motor neuron disease. Sci. Transl. Med. 7, 307ra153 (2015). sourceExperimental — accuracy not yet measured
The Results section (“HERV-K env transgenic animals develop motor dysfunction”; page not supplied) reports progressive motor dysfunction and a decrease in spontaneous excitatory postsynaptic current amplitude in mice expressing HERV-K env. It does not show those outcomes in mice expressing the entire HERV-K genome; the Results section reports whole-genome expression only in human neuronal cultures. “Decreases synaptic activity” is also broader than the specific synaptic measure that fell. (LLM, conf=0.84)
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Anti-retroviral reverse transcriptase inhibitors inhibit HERV-K activation in cultured cells43”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > DISCUSSION
What the sources say
- Partly supportedcites [43] Tyagi, R., Li, W., Parades, D., Bianchet, M. A. & Nath, A. Inhibition of human endogenous retrovirus-K by antiretroviral drugs. Retrovirology 14, 21 (2017). sourceExperimental — accuracy not yet measured
The Results section, “Inhibition of HERV-K by HIV-1 RT inhibitors” (page not available), reports that abacavir and zidovudine reduced HERV-K production in cultured HeLa cells after infection with pseudotyped HERV-K. This supports inhibition in cultured cells, but the experiment tested infection and viral production, not activation of endogenous HERV-K. (LLM, conf=0.82)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“double stranded RNAs produced by transposable element transcripts, including HERVs, can trigger a type I interferon response through the innate immune system44”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > DISCUSSION
What the sources say
- Could not verifycites [44] Chuong, E. B., Elde, N. C. & Feschotte, C. Regulatory evolution of innate immunity through co-option of endogenous retroviruses. Science 351, 1083–1087 (2016). sourceExperimental — accuracy not yet measured
The passages labeled Abstract describe ERV-derived enhancers that regulate genes after interferon stimulation, not double-stranded RNA produced by transposable-element transcripts triggering interferon production. Searches for double-stranded RNA, ERV transcripts, and innate immune sensing found no passage in our copy addressing that mechanism. (LLM, conf=0.77)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Could not verify
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and demonstrate that pathogenic tau causes active transposable element mobilization in neurons.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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- Probably not a substantial claim. 34
- It may state two separate claims as one. 23
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
“While transposable element activation has also been implicated in cancer6, and TDP-43 mediated neurodegeneration7–9, the extent to which transposable elements are involved in human disorders and drive disease pathogenesis is currently unknown.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > Abstract
What the sources say
- Not checked — no full text of the sourcecites [6] Burns, K. H. Transposable elements in cancer. Nat. Rev. Cancer 17, 415–424 (2017). source
- Supportedcites [7] Li, W., Jin, Y., Prazak, L., Hammell, M. & Dubnau, J. Transposable elements in TDP-43-mediated neurodegenerative disorders. PLoS One 7, e44099 (2012). source
The citation is attached to the statement that transposable element activation has been implicated in TDP-43-mediated neurodegeneration. The Introduction says the authors’ analyses led to the hypothesis that TE over-expression may contribute to that condition; the Abstract likewise presents the contribution as a hypothesis, consistent with uncertainty about its pathogenic role. (LLM, conf=0.92)
- Supportedcites [8] Li, W. et al. Human endogenous retrovirus-K contributes to motor neuron disease. Sci. Transl. Med. 7, 307ra153 (2015). source
In the citing sentence, references 7–9 attach to transposable element activation in TDP-43-mediated neurodegeneration, not to the following statement that the extent of involvement in human disorders is unknown. The Discussion reports that TDP-43 regulates HERV-K expression and that HERV-K activation causes neuronal injury, supporting the cited point. (LLM, conf=0.90)
- Supportedcites [9] Krug, L. et al. Retrotransposon activation contributes to neurodegeneration in a Drosophila TDP-43 model of ALS. PLoS Genet. 13, e1006635 (2017). source
The citation is attached to the preceding statement that transposable-element activation has been implicated in TDP-43-mediated neurodegeneration, not to the citing authors’ subsequent statement about what remains unknown in human disorders. The Discussion (page not available in our copy) identifies loss of retrotransposon silencing as a contributing factor in hTDP-43-related neurological deterioration in the Drosophila model. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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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
“Drosophila models of human tauopathy have progressive, age-associated neuronal death, a shortened lifespan, and decreased locomotor activity10,11.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Drosophila models of human tauopathy have altered levels of transposable element transcripts
What the sources say
- Partly supportedcites [10] Frost, B., Hemberg, M., Lewis, J. & Feany, M. B. Tau promotes neurodegeneration through global chromatin relaxation. Nat. Neurosci. 17, 357–366 (2014). sourceExperimental — accuracy not yet measured
The Results section ('Tau transgenic Drosophila have widespread alterations in chromatin structure'; page unavailable) says that human tau expression causes progressive neurodegeneration. The Results section ('Genetic manipulation of chromatin structure modifies tau neurotoxicity'; page unavailable) reports significantly decreased locomotor activity at ten days of age. Our copy does not establish a shortened lifespan or explicitly describe the neuronal death as age-associated. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [11] Wittmann, C. W. et al. Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science 293, 711–714 (2001). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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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
“While the function of piwi in regard to piRNA production and transposable element silencing is well established in the germline29, and piRNAs are known to exist in the Drosophila and mammalian brain30,31, it is currently unknown if piwi reduction affects transposable element transcripts in the brain.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Piwi/piRNA depletion is a mechanistic driver of transposable element transcription in tauopathy
What the sources say
- Partly supportedcites [30] Ghildiyal, M. et al. Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells. Science 320, 1077–1081 (2008). sourceExperimental — accuracy not yet measured
The passage describing Fig. 4C (indexed as Abstract; page unavailable) reports piRNA-like RNAs in Drosophila ago2-mutant heads. It does not establish that these are piRNAs in the brain, and the paper provides no evidence for piRNAs in mammalian brains. Its findings therefore support only a narrower part of the claim. (LLM, conf=0.82)
- Supportedcites [31] Lee, E. J. et al. Identification of piRNAs in the central nervous system. RNA 17, 1090–1099 (2011). source
The Abstract reports piRNAs in the mouse hippocampus, and the Discussion confirms their presence there. This supports the mammalian-brain portion of the jointly cited statement; the Drosophila-brain portion is not attributed to this source alone. (LLM, conf=0.92)
boosted- 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
“Tau-induced heterochromatin relaxation plays a causal role in mediating neurodegeneration, as loss of function mutations in Su(var)20533 and Su(var)3-934, genes encoding heterochromatin protein 1 (HP1) and a histone 3, lysine 9 methyltransferase, respectively, further deplete constitutive heterochromatin in tau transgenic Drosophila and enhance tau-induced neuronal death10.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Decondensation of heterochromatin contributes to aberrant transposable element transcription in the adult Drosophila brain
What the sources say
- Supportedcites [10] Frost, B., Hemberg, M., Lewis, J. & Feany, M. B. Tau promotes neurodegeneration through global chromatin relaxation. Nat. Neurosci. 17, 357–366 (2014). source
The Results section, “Genetic manipulation of chromatin structure modifies tau neurotoxicity,” reports that heterozygous loss-of-function alleles of Su(var)205 or Su(var)3-9 exacerbated heterochromatin loss in tau transgenic flies. It also reports double the neuronal apoptosis compared with flies expressing tau alone. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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
“Ectopic expression of proteins associated with aberrant activation of the cell cycle in post-mitotic neurons is a well-described feature of human tauopathy25.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Loss of transposable element silencing mediates tau-induced neurotoxicity in Drosophila.
What the sources say
- Supportedcites [25] Frost, B., Götz, J. & Feany, M. B. Connecting the dots between tau dysfunction and neurodegeneration. Trends Cell Biol. 25, 46–53 (2015). source
The “Double trouble – Cell cycle activation in postmitotic neurons in tauopathy” section (page not supplied) explicitly calls ectopic expression of cell-cycle markers in post-mitotic neurons, coincident with tau pathology, a well-described feature of tauopathies. The section also discusses human Alzheimer’s disease tissue, consistent with the claim’s human context. (LLM, conf=0.93)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- 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 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
“Since flamenco is known to encode a major piRNA cluster3,26, and piRNAs have recently been reported to be differentially expressed in the human Alzheimer’s disease brain27,28, we next determined if piRNAs are involved in dysfunctional transposable element control in the tauopathy brain.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Piwi/piRNA depletion is a mechanistic driver of transposable element transcription in tauopathy
What the sources say
- Not checked — no full text of the sourcecites [27] Roy, J., Sarkar, A., Parida, S., Ghosh, Z. & Mallick, B. Small RNA sequencing revealed dysregulated piRNAs in Alzheimer’s disease and their probable role in pathogenesis. Mol. Biosyst. 13, 565–576 (2017). source
- Supportedcites [28] Qiu, W. et al. Transcriptome-wide piRNA profiling in human brains of Alzheimer’s disease. Neurobiol. Aging 57, 170–177 (2017). source
The Results section ('Differential expression of piRNAs between cases and controls'; page not provided) reports 103 piRNAs nominally differentially expressed in human AD brain samples versus controls. The Discussion notes that most differential expressions did not survive Bonferroni correction, a qualification consistent with the citing sentence’s wording that differential expression was reported. (LLM, conf=0.93)
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
“Homozygous “permissive” loss of function alleles of flamenco allow transposable element mobilization and increase transposable element copy number within the Drosophila genome23,24.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Loss of transposable element silencing mediates tau-induced neurotoxicity in Drosophila.
What the sources say
- Not checked — no full text of the sourcecites [23] Pélisson, A. et al. About the origin of retroviruses and the co-evolution of the gypsy retrovirus with the Drosophila flamenco host gene. Genetica 100, 29–37 (1997). source
- Partly supportedcites [24] Mével-Ninio, M., Pelisson, A., Kinder, J., Campos, A. R. & Bucheton, A. The flamenco locus controls the gypsy and ZAM retroviruses and is required for Drosophila oogenesis. Genetics 175, 1615–1624 (2007). sourceExperimental — accuracy not yet measured
The paper states that homozygous permissive flamenco strains allow high levels of gypsy replicative transposition, and its Discussion reports that flamenco mutations remove repression of gypsy and ZAM. But the passage on gypsy copy number also says most permissive stocks remain stable because they lack functional gypsy proviruses. It therefore does not support an unqualified increase in transposable-element copy number. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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.
Every source the paper cites for this claim was checked and supports it.
In the paper
“In addition, neuronal phenotypes of tau transgenic Drosophila mimic features of human Alzheimer’s disease and associated tauopathies, including but not limited to aberrant tau phosphorylation13, oxidative stress14, DNA damage15,16, decondensation of constitutive heterochromatin10, synaptic dysfunction17 and activation of the cell cycle in post-mitotic neurons18.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Drosophila models of human tauopathy have altered levels of transposable element transcripts
What the sources say
- Supportedcites [10] Frost, B., Hemberg, M., Lewis, J. & Feany, M. B. Tau promotes neurodegeneration through global chromatin relaxation. Nat. Neurosci. 17, 357–366 (2014). source
Citation 10 is attached specifically to decondensation of constitutive heterochromatin, not to every phenotype in the sentence. In Results (“Tau transgenic Drosophila have widespread alterations in chromatin structure”; page not supplied), the paper reports reduced heterochromatin markers and diffuse staining in tau transgenic fly neurons. It also reports similar changes in human Alzheimer’s disease neurons (“Heterochromatin loss in vertebrate tauopathies”). (LLM, conf=0.94)
- Supportedcites [13] Steinhilb, M. L., Dias-Santagata, D., Fulga, T. A., Felch, D. L. & Feany, M. B. Tau phosphorylation sites work in concert to promote neurotoxicity in vivo. Mol. Biol. Cell 18, 5060–5068 (2007). source
Citation 13 is attached to aberrant tau phosphorylation, not to the other phenotypes in the list. The Results describe phosphorylation of disease-associated tau sites in transgenic flies, and the Discussion explicitly describes the Drosophila nervous system as mimicking aspects of human disease pathogenesis. (LLM, conf=0.91)
- Supportedcites [14] Dias-Santagata, D., Fulga, T. A., Duttaroy, A. & Feany, M. B. Oxidative stress mediates tau-induced neurodegeneration in Drosophila. J. Clin. Invest. 117, 236–245 (2007). source
The Introduction describes the tau-transgenic Drosophila model as recapitulating characteristics of human tauopathies. For the oxidative-stress feature marked by this citation, it states that oxidative stress plays a causal role in tau-induced neurodegeneration; the Results also report increased degeneration when antioxidant defenses are reduced. (LLM, conf=0.93)
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.
Probably not a substantial claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The flamenco locus harbors piRNAs that specifically degrade gypsy, Idefix, and ZAM transposable element transcripts24, among others.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Loss of transposable element silencing mediates tau-induced neurotoxicity in Drosophila.
What the sources say
- Partly supportedcites [24] Mével-Ninio, M., Pelisson, A., Kinder, J., Campos, A. R. & Bucheton, A. The flamenco locus controls the gypsy and ZAM retroviruses and is required for Drosophila oogenesis. Genetics 175, 1615–1624 (2007). sourceExperimental — accuracy not yet measured
The Results passage on P-element-induced mutations reports that flamenco is likely required for the accumulation of gypsy rasiRNAs, and the Discussion reports repression of gypsy and ZAM. Our copy does not establish that flamenco harbors piRNAs that directly degrade those transcripts, and the searched passages provide no support for Idefix. (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
“Like dietary restriction, 3TC is reported to reduce age-associated transposable element mobilization in the Drosophila fat body5”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Dietary restriction and inhibition of reverse transcriptase protect against tau-induced transposable element dysregulation and suppress neurotoxicity in tau transgenic Drosophila
What the sources say
- Supportedcites [5] Wood, J. G. et al. Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila. Proc. Natl. Acad. Sci. USA 113, 11277–11282 (2016). source
The Results section, “Pharmacological Suppression of Transposable Element Activity Delays Age-Related Transposition and Extends Life Span,” reports that 3TC-treated flies showed a significant delay in age-related transposition in the fat body compared with controls. This supports the claim that 3TC reduces age-associated transposable element mobilization there. (LLM, conf=0.94)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“that is FDA-approved for treatment of HIV/AIDS and Hepatitis B, both of which are caused by retroviruses”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Dietary restriction and inhibition of reverse transcriptase protect against tau-induced transposable element dysregulation and suppress neurotoxicity in tau transgenic Drosophila
What the sources say
- Partly supportedcites [38] Coates, J. A. et al. (–)-2′-Deoxy-3′-thiacytidine is a potent, highly selective inhibitor of human immunodeficiency virus type 1 and type 2 replication in vitro. Antimicrob. Agents Chemother. 36, 733–739 (1992). sourceExperimental — accuracy not yet measured
The Discussion reports that 3TC inhibits HIV-1 and HIV-2 replication in vitro and calls it a candidate for AIDS treatment, with clinical trials in progress. It does not support the claim that 3TC was FDA-approved or used to treat hepatitis B, nor does it classify hepatitis B as a retroviral disease. (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
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“3TC (Lamivudine) is a water-soluble nucleoside analog inhibitor of reverse transcriptase38”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Dietary restriction and inhibition of reverse transcriptase protect against tau-induced transposable element dysregulation and suppress neurotoxicity in tau transgenic Drosophila
What the sources say
- Partly supportedcites [38] Coates, J. A. et al. (–)-2′-Deoxy-3′-thiacytidine is a potent, highly selective inhibitor of human immunodeficiency virus type 1 and type 2 replication in vitro. Antimicrob. Agents Chemother. 36, 733–739 (1992). sourceExperimental — accuracy not yet measured
The introduction identifies 3TC as a nucleoside analog, and the Discussion says its triphosphate form is assumed to inhibit viral reverse transcriptase; the paper presents its data as consistent with that mechanism. Our copy does not state that 3TC is water-soluble, and it does not directly establish reverse-transcriptase inhibition. (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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Elevated HERV-K transcripts are associated with amyotrophic lateral sclerosis (ALS)8 and many human cancers, including melanoma, breast cancer, germ cell tumors, renal cancer, and ovarian cancer42”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > DISCUSSION
What the sources say
- Supportedcites [8] Li, W. et al. Human endogenous retrovirus-K contributes to motor neuron disease. Sci. Transl. Med. 7, 307ra153 (2015). source
Citation 8 is attached to the ALS portion of the sentence; the cancer portion has a separate citation, 42. In Results, “HERV-K is expressed in the brain tissue of ALS patients” (page not supplied), the paper reports elevated HERV-K transcripts in postmortem brain tissue from patients with ALS. (LLM, conf=0.93)
- Partly supportedcites [42] Gonzalez-Cao, M. et al. Human endogenous retroviruses and cancer. Cancer Biol. Med. 13, 483–488 (2016). sourceExperimental — accuracy not yet measured
Citation 42 is attached to the cancer examples, while ALS has a separate citation. In “Expression of HERVs in cancer cells” (page unavailable), the paper reports elevated HERV-K-containing mRNA in breast cancer patients and HERV-K protein in several cancers, but it does not establish elevated HERV-K transcripts across all the listed cancers; the renal-cancer transcripts it identifies are HERV-E. (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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“reduces age-related transposable element mobilization events in the Drosophila fat body5”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Dietary restriction and inhibition of reverse transcriptase protect against tau-induced transposable element dysregulation and suppress neurotoxicity in tau transgenic Drosophila
What the sources say
- Supportedcites [5] Wood, J. G. et al. Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila. Proc. Natl. Acad. Sci. USA 113, 11277–11282 (2016). source
The Abstract (page not provided) reports that dietary restriction delayed the age-associated increase in transposable-element transposition in fly fat body cells. The Discussion likewise says dietary restriction suppressed the age-related increase in TE mobilization. (LLM, conf=0.94)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In this study, we also excluded 9 cortex and 15 cerebellum samples that had an RNA Integrity Number (RIN)63 less than 7.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > ONLINE METHODS > Analysis of human RNA-seq data.
What the sources say
- Supportedcites [63] Schroeder, A. et al. The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol. Biol. 7, 3 (2006). source
The citation is attached to “RNA Integrity Number (RIN),” identifying the measure used by the citing study. The source paper’s Discussion describes the development of the RNA Integrity Number algorithm. The sample exclusions and cutoff are the citing study’s own methods, not findings attributed to this source. (LLM, conf=0.92)
plainn = 15- 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
“Sample sizes are similar to or greater than those reported in previous publications4,5,10.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > ONLINE METHODS > Statistical analyses.
What the sources say
- Supportedcites [4] Li, W. et al. Activation of transposable elements during aging and neuronal decline in D rosophila. Nat. Neurosci. 16, 529–531 (2013). source
The Online Methods report sample sizes of approximately 50–150 flies per genotype for lifespan measurements and 50–100 flies per group for behavioral training (pages not specified). These are sample sizes from the cited previous publication; the comparison with the citing authors’ own samples is their assessment, not a statement attributed to this source. (LLM, conf=0.83)
- Partly supportedcites [5] Wood, J. G. et al. Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila. Proc. Natl. Acad. Sci. USA 113, 11277–11282 (2016). sourceExperimental — accuracy not yet measured
The SI Materials and Methods, “Life Span Assays” (page unavailable), reports at least 250 flies per condition; “RNA-seq” (page unavailable) reports at least three biological replicates per condition. These establish sample sizes for this previous publication, but our copy cannot establish whether the citing study’s sample sizes are similar or greater. (LLM, conf=0.78)
- Supportedcites [10] Frost, B., Hemberg, M., Lewis, J. & Feany, M. B. Tau promotes neurodegeneration through global chromatin relaxation. Nat. Neurosci. 17, 357–366 (2014). source
The Online Methods, Statistical Analysis section says the authors’ sample sizes were similar to those reported in previous publications. That supports the citing sentence’s inclusive wording, “similar to or greater than.” (LLM, conf=0.92)
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
Every source the paper cites for this claim was checked and supports it.
In the paper
“Dietary restriction extends lifespan in invertebrate and vertebrate systems36”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Dietary restriction and inhibition of reverse transcriptase protect against tau-induced transposable element dysregulation and suppress neurotoxicity in tau transgenic Drosophila
What the sources say
- Supportedcites [36] Longo, V. D. et al. Interventions to slow aging in humans: are we ready? Aging Cell 14, 497–510 (2015). source
The “Intermittent and prolonged fasting” section (page not provided) identifies fasting as a dietary-restriction intervention and reports lifespan extension in worms and rodents. Those examples support the claim for invertebrate and vertebrate systems. (LLM, conf=0.92)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Based on current understanding, cells have two layers of defense against potentially deleterious transposable element activation: 1) Transposable element transcription is limited by heterochromatin-mediated silencing, and 2) Transposable element transcripts are cleared from the cell by piRNA-mediated degradation”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [3] Brennecke, J. et al. Discrete small RNA-generating loci as master regulators of transposon activity in D rosophila. Cell 128, 1089–1103 (2007). source
- Partly supportedcites [39] Andersen, P. R., Tirian, L., Vunjak, M. & Brennecke, J. A heterochromatin-dependent transcription machinery drives piRNA expression. Nature 549, 54–59 (2017). sourceExperimental — accuracy not yet measured
The Abstract and Discussion (pages unavailable) support heterochromatin-mediated repression of transposon transcription. The Abstract also says the piRNA pathway targets transposons post-transcriptionally, but our copy does not specify that this clears their transcripts through degradation. (LLM, conf=0.83)
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.
Probably not a substantial claim. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Dietary restriction and 3TC (lamivudine), a nucleoside analog inhibitor of reverse transcriptase that is FDA-approved for the treatment of HIV and Hepatitis B, suppress tau-induced transposable element dysregulation and tau-induced neurotoxicity.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > Abstract
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For several subgroups of transposable elements, we found that multiple members of the same subgroup, such as copia, HeT-A, and Quasimodo, are increased in tauR406W transgenic Drosophila, while members of other subgroups, such as Burdock and Blood, are decreased in tauR406W transgenic Drosophila.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Drosophila models of human tauopathy have altered levels of transposable element transcripts
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We identified 50 transposable elements that are significantly increased at the transcript level in tau transgenic Drosophila compared to controls, and 60 transposable elements that are significantly decreased”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Drosophila models of human tauopathy have altered levels of transposable element transcripts
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two different heterozygous loss of function alleles of flamenco23,24 do not induce neuronal death or locomotor deficits in controls, but significantly enhance neuronal death in tauR406W transgenic Drosophila (Fig. 2a) and exacerbate tau-induced locomotor deficits (Fig. 2b).”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Loss of transposable element silencing mediates tau-induced neurotoxicity in Drosophila.
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.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“14 of 25 probes were confirmed by NanoString as significantly increased (Fig. 1c), while 6 of 22 probes were confirmed as significantly decreased in heads of tauR406W transgenic Drosophila (Fig. 1d).”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Drosophila models of human tauopathy have altered levels of transposable element transcripts
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.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pan-neuronal expression of tauWT significantly increases 10 of 25, and decreases 8 of 22 probes recognizing transposable elements that were identified as increased or decreased, respectively, in tauR406W Drosophila based on RNA-seq (Supplementary Fig. 2b, c)”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Drosophila models of human tauopathy have altered levels of transposable element transcripts
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we found that specific subgroups of transposable elements are upregulated in human tauopathy, while other subgroups are downregulated”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Aberrant transposable element transcription in human tauopathy
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.
- Rests on an assumption: The human postmortem RNA-seq data accurately reflect antemortem transposable element expression.
- Rests on an assumption: Differences in transposable element expression between tauopathy and control are not due to differences in cell-type composition.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We performed a similar analysis on cerebellum, which showed that 20 transposable elements have variable expression in Alzheimer’s disease, progressive supranuclear palsy, or control (Supplementary Fig. 4a, b, c, Supplementary Table 7).”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > ONLINE METHODS > Principal component analyses (PCA) of human RNA-seq data.
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In particular, the majority of control samples are below the orange diagonal line.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > ONLINE METHODS > Principal component analyses (PCA) of human RNA-seq data.
plainn = 75- 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 result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While NanoString data show a similar expression trend of most of the transposable elements that are identified as differentially expressed in tau transgenic Drosophila by RNA-seq, some of the elements are not confirmed as differentially expressed by NanoString”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > DISCUSSION
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.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We identify genetic, dietary and pharmacological approaches to reduce transposable element dysregulation and suppress tau-induced neurotoxicity in Drosophila”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > DISCUSSION
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.
A result the paper reports from its own data — 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, analyses of human transposable elements clearly reveal a significant transcriptional increase in endogenous retroviruses, and a significant decrease in non-LTR retroelements in postmortem human brain of both Alzheimer’s disease and progressive supranuclear palsy patients”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Aberrant transposable element transcription in human tauopathy
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.
It may state two separate claims as one.
- Rests on an assumption: The human postmortem RNA-seq data accurately reflect antemortem transposable element expression.
- Rests on an assumption: Differences in transposable element expression between tauopathy and control are not due to differences in cell-type composition.
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, our studies identify heterochromatin decondensation and depletion of piwi and piRNAs as key mechanisms driving transposable element dysregulation and subsequent neuronal death in tau-mediated neurodegeneration.”
- Also stated in: § Abstract · boosted
“Taken together, our data identify heterochromatin decondensation, piwi/piRNA depletion and consequent transposable element dysregulation as a novel, pharmacologically targetable, mechanistic driver of neurodegeneration in tauopathy.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > Abstract
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.
- Also stated in: § Abstract · boosted
In the paper
“Many transposable elements are embedded within highly condensed constitutive heterochromatin, and are thus epigenetically silenced2.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > Abstract
What the sources say
- Not checked — no full text of the sourcecites [2] Slotkin, R. K. & Martienssen, R. Transposable elements and the epigenetic regulation of the genome. Nat. Rev. Genet. 8, 272–285 (2007). 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.
In the paper
“In addition, transposable element transcripts are the targets of a well-conserved pathway involving piRNAs, small regulatory RNAs that bind to transposable element transcripts and mediate their degradation3.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > Abstract
What the sources say
- Not checked — no full text of the sourcecites [3] Brennecke, J. et al. Discrete small RNA-generating loci as master regulators of transposon activity in D rosophila. Cell 128, 1089–1103 (2007). source
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.
Probably not a substantial claim.
In the paper
“Based on previous studies that identified constitutive heterochromatin as a silencing mechanism for transposable elements35, we next determined if genetically promoting heterochromatin relaxation affects the transposable elements that are differentially expressed in tau transgenic Drosophila.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Decondensation of heterochromatin contributes to aberrant transposable element transcription in the adult Drosophila brain
What the sources say
- Not checked — no full text of the sourcecites [35] Fedoroff, N. V. Presidential address. Transposable elements, epigenetics, and genome evolution. Science 338, 758–767 (2012). source
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.
Probably not a substantial claim.
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
“The complexity and repetitive nature of transposable elements presents challenges to RNA-seq analysis, which is associated with a greater frequency of false positives and negatives compared to analysis of canonical messenger RNAs.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Drosophila models of human tauopathy have altered levels of transposable element transcripts
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.
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, our data identify heterochromatin decondensation, piwi/piRNA depletion and consequent transposable element dysregulation as a novel, pharmacologically targetable, mechanistic driver of neurodegeneration in tauopathy.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > Abstract
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.
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
“Based on PCNA staining, pan-neuronal piwi reduction is also sufficient to activate the cell cycle in neurons (Supplementary Fig. 4b), suggesting that pathogenic tau acts through piwi reduction to mediate aberrant cell cycle activation and consequent neuronal death.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Piwi/piRNA depletion is a mechanistic driver of transposable element transcription in tauopathy
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.
- Rests on an assumption: piwi is a central regulator of piRNA biogenesis.
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 piwi reduction depletes piRNAs, which significantly increases transposable element transcripts and causally contributes to tau-induced neurotoxicity.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Piwi/piRNA depletion is a mechanistic driver of transposable element transcription in tauopathy
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.
- Rests on an assumption: piwi is a central regulator of piRNA biogenesis.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Since flamenco is known to encode a major piRNA cluster3,26, and piRNAs have recently been reported to be differentially expressed in the human Alzheimer’s disease brain27,28, we next determined if piRNAs are involved in dysfunctional transposable element control in the tauopathy brain.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Piwi/piRNA depletion is a mechanistic driver of transposable element transcription in tauopathy
What the sources say
- Not checked — no full text of the sourcecites [3] Brennecke, J. et al. Discrete small RNA-generating loci as master regulators of transposon activity in D rosophila. Cell 128, 1089–1103 (2007). source
- Not checked — no full text of the sourcecites [26] Sarot, E., Payen-Groschêne, G., Bucheton, A. & Pélisson, A. Evidence for a piwi-dependent RNA silencing of the gypsy endogenous retrovirus by the Drosophila melanogaster flamenco gene. Genetics 166, 1313–1321 (2004). source
boosted- 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.
In the paper
“While the function of piwi in regard to piRNA production and transposable element silencing is well established in the germline29, and piRNAs are known to exist in the Drosophila and mammalian brain30,31, it is currently unknown if piwi reduction affects transposable element transcripts in the brain.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Piwi/piRNA depletion is a mechanistic driver of transposable element transcription in tauopathy
What the sources say
- Not checked — no full text of the sourcecites [29] Siomi, M. C., Sato, K., Pezic, D. & Aravin, A. A. PIWI-interacting small RNAs: the vanguard of genome defence. Nat. Rev. Mol. Cell Biol. 12, 246–258 (2011). source
boosteddirect- 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
“Rather than a general effect on the panel of transposable elements that are dysregulated by pathogenic tau, these analyses suggest that enhancement of tau-induced neurotoxicity by flamenco loss of function is due to activation of specific elements affected by pathogenic tau, and/or additional elements outside of our NanoString codeset.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Loss of transposable element silencing mediates tau-induced neurotoxicity in Drosophila.
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 claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“12 cortex (syn6126114) and 10 cerebellum (syn6126119) samples were excluded due to low quality61,62.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > ONLINE METHODS > Analysis of human RNA-seq data.
What the sources say
- Not checked — no full text of the sourcecites [61] Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007). source
- Not checked — no full text of the sourcecites [62] Price, A. L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006). source
plainn = 10- 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.
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
“Equal loading was assessed by Ponceau S staining.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > ONLINE METHODS > Western blotting.
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.
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
“After this filtering, 80 Alzheimer’s disease, 82 progressive supranuclear palsy, and 21 control cortex samples were available, as well as 76 Alzheimer’s disease, 78 progressive supranuclear palsy, and 25 control cerebellum samples.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > ONLINE METHODS > Analysis of human RNA-seq data.
plainn = 21- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim.
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
“Experiments utilizing the gypsy-TRAP reporter or flamenco require two genetic elements on the X chromosome, thus all data points are from female flies.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > ONLINE METHODS > Drosophila genetics.
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.
In the paper
“Like retroviruses, retrotransposons encode machinery, including a capsid protein, polymerase, integrase, and reverse transcriptase, needed to copy themselves and insert the new copy into the genome37”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Dietary restriction and inhibition of reverse transcriptase protect against tau-induced transposable element dysregulation and suppress neurotoxicity in tau transgenic Drosophila
What the sources say
- Not checked — no full text of the sourcecites [37] Sultana, T., Zamborlini, A., Cristofari, G. & Lesage, P. Integration site selection by retroviruses and transposable elements in eukaryotes. Nat. Rev. Genet. 18, 292–308 (2017). source
plain- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
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
“After this filtering, 80 Alzheimer’s disease, 82 progressive supranuclear palsy, and 21 control cortex samples were available, as well as 76 Alzheimer’s disease, 78 progressive supranuclear palsy, and 25 control cerebellum samples.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > ONLINE METHODS > Analysis of human RNA-seq data.
plainn = 25- 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.
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
“An equal number of males and females were used in all Drosophila assays with the exception of gypsy-TRAP and flamenco genetic manipulations.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > ONLINE METHODS > Drosophila genetics.
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.
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
“The quality of bases in the cleaned reads was above 28 (Sanger/Illumina 1.9 encoding).”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > ONLINE METHODS > RNA sequencing and data analyses.
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.
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
“Samples were randomized in all Drosophila studies.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > ONLINE METHODS > Statistical analyses.
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.
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
“Investigators were blinded to genotype in all immunohistochemistry, immunofluorescence, and locomotor activity assays.”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > ONLINE METHODS > Statistical analyses.
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.
The paper relies on this without support.
It is currently unknown whether piwi reduction affects transposable element transcripts in the brain.
“it is currently unknown if piwi reduction affects transposable element transcripts in the brain.”
The paper relies on this without support.
Neuronal death in Drosophila models of tauopathy is age-dependent.
“Neuronal death in Drosophila models of tauopathy is age-dependent.”
The paper relies on this without support.
piwi is a central regulator of piRNA biogenesis.
“In addition, protein levels of piwi, a central regulator of piRNA biogenesis, are depleted in brains of tau transgenic Drosophila based on both immunofluorescence (Fig. 3b) and western blotting (Fig. 3c).”
The paper relies on this without support.
The protective effects of 3TC are mediated by inhibition of reverse transcriptase.
“Tau transgenic flies treated with 10 mM 3TC have significantly reduced gypsy-TRAP reporter activation in the brain (Fig. 6a, b)”
The paper relies on this without support.
The human postmortem RNA-seq data accurately reflect antemortem transposable element expression.
“We next analyzed transposable element expression in human tauopathy using RNA-seq data from cortex (Fig. 7a, b) and cerebellum (Supplementary Fig. 8a, b) of postmortem human control, Alzheimer’s disease, and progressive supranuclear palsy patients”
The paper relies on this without support.
Differences in transposable element expression between tauopathy and control are not due to differences in cell-type composition.
“we found that specific subgroups of transposable elements are upregulated in human tauopathy, while other subgroups are downregulated”
The authors state this as an assumption.
Data distribution was assumed to be normal but this was not formally tested.
“Data distribution was assumed to be normal but this was not formally tested.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Expression of a disease-associated human Tau protein in Drosophila neurons elicited loss of H3K9me2, widespread retrotransposon activation, DNA damage, and neuronal cell death that could be rescued with NRTIs139.”
From The role of retrotransposable elements in ageing and age-associated diseases (2021) · cites this paper as [139]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Postmortem AD brain samples exhibited increased markers of open chromatin137 and elevated expression of retrotransposons138, 139.”
From The role of retrotransposable elements in ageing and age-associated diseases (2021) · cites this paper as [139]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Depletion of piwi proteins was shown to increase transposable element (TE) transcription in a Drosophila model of tauopathy (77).”
From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [77]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“suppression of RTE was shown to reduce tau activation and tau-induced neurotoxicity in tau transgenic Drosophila (77).”
From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [77]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Leveraging RNA-seq data from the Accelerating Medicines Partnership–Alzheimer's Disease (AMP-AD) project, the Frost group (Sun et al. 2018) discovered that retrotransposons, particularly of the HERV class, are elevated in brains of patients with AD and progressive supranuclear palsy (PSP), a primary tauopathy, compared to controls.”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Sun et al. 2018
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Using a fluorescence-based reporter of de novo TE insertion (Li et al. 2013), Sun et al. (2018) found that pan-neuronal expression of transgenic human tau induced transposition in adult neurons of the Drosophila brain.”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Sun et al. 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Among retrotransposons that are transcriptionally elevated in human AD and PSP, most are no longer active (Guo et al. 2018, Sun et al. 2018).”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Sun et al. 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Studies in Drosophila indicate that the negative effects of tau on the lamin nucleoskeleton result in the decondensation of heterochromatin (Frost et al. 2014) and a toxic, neuroinflammatory activation of retrotransposons (Ochoa et al. 2023, Sun et al. 2018).”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Sun et al. 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Of note, transposable element activation in AD is preferentially associated with tau pathology, consistently with findings from a Drosophila tauopathy model [124].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [124]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Both interventions were found to reduce neurodegeneration, suggesting that the generation of new retrotransposon DNA copies is neurotoxic.”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Sun et al. 2018
The cited source says what the claim attributes to it.
In the citing paper
“Studies in tau transgenic Drosophila suggest that TEs are indeed capable of full retrotransposition.”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Sun et al. 2018
The cited source says what the claim attributes to it.
In the citing paper
“Such transposition could be suppressed via caloric restriction or pharmacological blockage of reverse transcription.”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Sun et al. 2018
The cited source says what the claim attributes to it.
In the citing paper
“In tau transgenic Drosophila, the nucleoside analog reverse transcriptase inhibitor (NRTI) 3TC reduces tau-induced retrotransposition and neurodegeneration (Sun et al. 2018).”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Sun et al. 2018
The cited source says what the claim attributes to it.
In the citing paper
“In addition to tau-induced decondensation of heterochromatin, brains of tau transgenic Drosophila were found to have significantly decreased levels of Piwi and piRNAs.”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Sun et al. 2018
The cited source says what the claim attributes to it.
In the citing paper
“Several groups have independently detected elevated TE transcripts in human AD [122–124], adding to an intriguing phenomenon of TE dysregulation in neurodegenerative diseases [125–128].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [124]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Aberrant transposable element transcription in human tauopathy
“cerebellum (Supplementary Fig. 8a, b)”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > ONLINE METHODS > Principal component analyses (PCA) of human RNA-seq data.
“We performed a similar analysis on cerebellum, which showed that 20 transposable elements have variable expression in Alzheimer’s disease, progressive supranuclear palsy, or control (Supplementary Fig. 4a, b, c, Supplementary Table 7).”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > ONLINE METHODS > Dietary restriction and 3TC treatment.
“3TC (Fisher, #50731692, 10 mM except in Supplementary Fig. 3)”
§ Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies > RESULTS > Dietary restriction and inhibition of reverse transcriptase protect against tau-induced transposable element dysregulation and suppress neurotoxicity in tau transgenic Drosophila
“3TC treatment significantly reduces tau-induced neuronal death (Fig. 6c), and significantly alleviates tau-induced locomotor deficits (Fig. 6d) in a dose-dependent manner (Supplementary Fig. 7a, b).”
Citations
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“Another study reported that tau-induced depletion of piRNAs led to neuronal mortality via transposable element dysregulation in tau-related neuro-degenerative disease [25].”
BackgroundBeckmann, A., Ramirez, P., Gamez-Guijarro, M., Gonzalez, E. M., Mange, J. D., Bieniek, K. F., Ray, W. J., & Frost, B. E. (2023) · iScience · doi:10.1016/j.isci.2023.106152 · Cited by 24
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“Finally, the only study to analyze HERV expression in PD showed no detection of HERV-K pol transcripts in PD brain tissues [76], suggesting the alterations in genomic HERVs may not translate into proteins.”
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“Furthermore, pathogenic tau induced the reduction of piRNAs in tau-related neurodegenerative diseases such as AD and progressive supranuclear palsy and consequently caused abnormal transposable element activity and subsequently progressive neuronal death (Sun et al., 2018).”
BackgroundPiWi RNA in Neurodevelopment and Neurodegenerative Disorders
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“Transposable element dysregulation has been found to cause neuronal death in tauopathies such as AD (W. Sun et al., 2018).”
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“Two other studies also show that a significant alteration of transposon expression in human and fly tauopathy brains, implicating that dysregulation of transposons in heterochromatin may cause neurotoxicity [52,53].”
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“This study revealed a significant upregulation of several human endogenous retroviruses in the disease context (Sun et al., 2018).”
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“Tau may be involved in chromatin remodeling around HERV sequences, making regions in which HERVs are found increasingly transcriptionally accessible (Sun et al., 2018).”
BackgroundTaming transposable elements in livestock and poultry: a review of their roles and applications
Zhao, P., Peng, C., Fang, L., Wang, Z., & Liu, G. E. (2023) · Genetics Selection Evolution · doi:10.1186/s12711-023-00821-2 · Cited by 27
“Transposable elements can also serve as an important source of functional lncRNA and small non-coding RNA (miRNA and siRNA) [149, 150].”
BackgroundHuang, X., Wang, C., Zhang, T., Li, R., Chen, L., Leung, K. L., Lakso, M., Zhou, Q., Zhang, H., & Wong, G. (2023) · Nature Communications · doi:10.1038/s41467-023-41881-8 · Cited by 21
Epigenetic modifications of DNA and RNA in Alzheimer’s disease
Martínez-Feduchi, P., Jin, P., & Yao, B. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1398026 · Cited by 22
PIWI family proteins as prognostic markers in cancer: a systematic review and meta-analysis
Mentis, A. A., Dardiotis, E., Romas, N. A., & Papavassiliou, A. G. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03403-y · Cited by 19
Cabral, G. F., Schaan, A. P., Cavalcante, G. C., Sena-dos-Santos, C., de Souza, T. P., Port’s, N. M. D. S., Pinheiro, J. A. D. S., Ribeiro‐dos‐Santos, Â., & Vidal, A. F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189839 · Cited by 18
“It was also reported that pathogenic Tau protein leads to a decrease in piRNA-mediated regulation, which increases TE retrotransposition in PD neurons, triggering oxidative stress and cell death [84,85].”
BackgroundPiwi/piRNAs control food intake by promoting neuropeptide F expression in locusts
Wang, H., Jiang, F., Liu, X., et al. (2022) · EMBO Reports · doi:10.15252/embr.202050851 · Cited by 18
Schlachetzki, J. C. M., Toda, T., & Mertens, J. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.110876 · Cited by 18
“In addition, in a model for Alzheimer’s disease pathology in Drosophila melanogaster and in human neurons from AD cases, Lamin-dependent nuclear architecture and gene repression were disrupted (Frost et al., 2016; 2014; Sun et al., 2018).”
BackgroundRavel‐Godreuil, C., Massiani-Beaudoin, O., Mailly, P., Prochiantz, A., Joshi, R. L., & Fuchs, J. (2021) · iScience · doi:10.1016/j.isci.2021.102756 · Cited by 24
Epigenetics in Neurodegenerative Diseases
van Zundert, B., & Montecino, M. A. (2025) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-031-75980-2_3 · Cited by 18
Snowbarger, J. M., Koganti, P., & Spruck, C. (2024) · Biomolecules · doi:10.3390/biom14101250 · Cited by 14
“Several recent studies have shown elevated expression of TEs (i.e., HERVs, ALUs, LINE-1) in the brains of AD patients [162–165].”
BackgroundPIWI-interacting RNAs in human diseases: databases and computational models
Zhang, T., Chen, L., Li, R., Liu, N., Huang, X., & Wong, G. (2022) · Briefings in Bioinformatics · doi:10.1093/bib/bbac217 · Cited by 16
Yang, Y., Wen, X., Wu, Z., Wang, K., & Zhu, Y.-X. (2023) · Science China Life Sciences · doi:10.1007/s11427-022-2341-8 · Cited by 11
“…initiate transcription in the host genome, and these novel TSSs were found to originate a set of long noncoding RNAs and/or novel transcript isoforms of conserved protein-coding genes during human and mouse evolution (Cowley and Oakey, 2013; Jang et al., 2019; Miao et al., 2020; Sun et al., 2018).”
BackgroundKiparaki, M., & Baker, N. E. (2023) · Genetics · doi:10.1093/genetics/iyad080 · Cited by 17
Bei, J., Miranda-Morales, E. G., Gan, Q., Qiu, Y., Husseinzadeh, S., Liew, J. Y., Chang, Q., Krishnan, B., Gaitas, A., Yuan, S., et al. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230347 · Cited by 18
“There has been increased interest in studying the potential of EVs in AD[64–66], mainly focusing on theirproteincontents[67–72].”
Exosomes in the Diagnosis of Neuropsychiatric Diseases: A Review
Wu, S., Shang, X.-M., Guo, M., Su, L., & Wang, J. (2024) · Biology · doi:10.3390/biology13060387 · Cited by 16
“Researchers need to manage and store sample information appropriately and ensure that the participant recruitment process is fair and equitable.”
BackgroundCapsid transfer of the retrotransposon Copia controls structural synaptic plasticity in Drosophila
M'angale, P. G., Lemieux, A., Liu, Y., Wang, S., Zinter, M., Alegre, G., Simkin, A., Budnik, V., Kelch, B. A., & Thomson, T. (2025) · PLoS Biology · doi:10.1371/journal.pbio.3002983 · Cited by 16
Tau mRNA Metabolism in Neurodegenerative Diseases: A Tangle Journey
da Costa, P. J., Hamdane, M., Buée, L., & Martin, F. (2022) · Biomedicines · doi:10.3390/biomedicines10020241 · Cited by 16
“Besides affecting microtubule dynamics, pathogenic forms of tau are reported to affect nuclear pore localization, function and nucleocytoplasmic trafficking [19,20], induce heterochromatin relaxation [21], promote DNA damage [22,23], alter RNA stability and RNA export [24–26], promote ribosome instability [27] and act…”
BackgroundPIWI-Interacting RNAs: A Pivotal Regulator in Neurological Development and Disease
Pan, X. M., Dai, W., Wang, Z., Li, S., Sun, T., & Miao, N. (2024) · Genes · doi:10.3390/genes15060653 · Cited by 14
“It includes two primary loop and the ping-pong loop (Figure 1) [30, Genes 2024 , 15 , x FOR PEER REVIEW 2 of 19 neurodevelopmental and neurodegenerative activities [20,24,25,27].”
BackgroundInfluentialRecent advances of PIWI‐interacting RNA in cardiovascular diseases
Li, B., Wang, K., Cheng, W., Fang, B., Li, Y. H., Yang, S. M., Zhang, M. H., Wang, Y., & Wang, K. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.1770 · Cited by 15
“37,38 In addition, the expression of some piRNAs is abnormal in Alzheimer’s disease patients.”
BackgroundEmerging Connections Between Tau and Nucleic Acids
Galas, M., Bonnefoy, E., Buée, L., & Lefebvre, B. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-32-9358-8_12 · Cited by 17
Intercellular viral spread and intracellular transposition of Drosophila gypsy
Keegan, R. M., Talbot, L. R., Chang, Y.-H., Metzger, M. J., & Dubnau, J. (2021) · PLOS Genetics · doi:10.1371/journal.pgen.1009535 · Cited by 14
“Although functional consequences of RTE replication during normal neural development are not established, there is growing evidence that dysfunctional expression has a detrimental impact on organismal fitness during aging [11,16,26–37] and in age-related diseases such as cancer [38–52], autoimmune disorders [53– 55] a…”
BackgroundBonham, L. W., Geier, E. G., Sirkis, D. W., Leong, J. K., Ramos, E. M., Wang, Q., Karydas, A., Lee, S. E., Sturm, V. E., Sawyer, R. P., et al. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.1448-22.2022 · Cited by 15
Bughio, F., & Maggert, K. A. (2018) · Chromosome Research · doi:10.1007/s10577-018-9591-2 · Cited by 15
“Ribosomal DNA expression, rDNA loss, nucleolus-mediated stress responses, and heterochromatin defects are now being connected to neurological diseases (Jesse et al. 2017; Maina et al. 2018; Nunez Villacis et al. 2018; Sun et al. 2018)—whether these are confirmed, or are found to be consequential to the disease, remain…”
Unexplored power of CRISPR-Cas9 in neuroscience, a multi-OMICs review
Banazadeh, M., Abiri, A., Poortaheri, M. M., Asnaashari, L., Langarizadeh, M. A., & Forootanfar, H. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.130413 · Cited by 12
Znaidi, R., Massiani-Beaudoin, O., Mailly, P., Monnet, H., Bonnifet, T., The Brainbank Neuro-CEB Neuropathology Network, Joshi, R. L., & Fuchs, J. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149579 · Cited by 14
“In recent years, TEs have emerged as possible new pathogenic players in NDs (Blaudin de Th ´ e et al., 2018; Li et al., 2012; Sun et al., 2018; Rekaik et al., 2015; Peze-Heidsieck et al., 2022; Casale et al., 2021; Tam et al., 2019; Ravel-Godreuil et al., 2021).”
InfluentialDudzik, J., Czechowicz, P., Więch, A., Sławski, J., Collawn, J. F., & Bartoszewski, R. (2025) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.70012 · Cited by 13
“The hypothesis put forward is that “Tau pathology” may have a feedback influence on piRNAs, and its disruption may reflect a general genome instability that leads to the development and progression of AD (Frost et al. 2014; Sun et al. 2018; Jain et al. 2019).”
The piRNA pathway in planarian flatworms: new model, new insights
Kim, I. V., Riedelbauch, S., & Kuhn, C. (2020) · Biological Chemistry · doi:10.1515/hsz-2019-0445 · Cited by 11
Sarkar, S., & Feany, M. Β. (2021) · Toxicological Sciences · doi:10.1093/toxsci/kfab060 · Cited by 12
Silverman, M. H., Duggan, S., Bardelli, G., Sadler, B., Key, C., Medlock, M., Reynolds, L., & Wallner, B. (2022) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2022.71 · Cited by 12
“Major pathological features of AD include cerebral plaques laden with beta-amyloid peptides, degeneration of neurites in neocortical terminals, medial temporal-lobe structures containing prominent neurofibrillary tangles, aggregation of phosphorylated tau, inflammation, oxidative damage, loss of neurons leading to los…”
BackgroundOverwintering conditions impact insulin pathway gene expression in diapausing Megachile rotundata
Cambron, L. D., Yocum, G. D., Yeater, K. M., et al. (2021) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2021.110937 · Cited by 12
Navigating the brain and aging: exploring the impact of transposable elements from health to disease
Breton, A. L., Bettencourt, M. P., & Gendrel, A.-V. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1357576 · Cited by 12
Viruses and the Brain—A Relationship Prone to Trouble
Mielcarska, M. B., & Rouse, B. T. (2025) · Viruses · doi:10.3390/v17020203 · Cited by 15
“AD HERV-H, HERV-K, HERV-L, HERV-W [5,470] progressive supranuclear palsy HERV-H, HERV-K, HERV-L [470] FTD HERV-K [471] PD HERV-K [5,472] However, the mechanistic circumstance that precipitates such events is poorly understood.”
Widespread transposable element dysregulation in human aging brains with Alzheimer's disease
Feng, Y., Yang, X. J., Hou, Y., Zhou, Y., Leverenz, J. B., Eng, C., Pieper, A. A., Goate, A., Shen, Y., & Cheng, F. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14164 · Cited by 11
“84 Impaired activation of TEs has been associatedwithweakinterferonresponseinSARS-CoV-2humancellu-larmodels, 85 suggestingthatdecreasedTEexpressioncouldalsoaffect host immune response.”
Alterations of mRNAs and Non-coding RNAs Associated with Neuroinflammation in Alzheimer’s Disease
Hernández-Contreras, K. A., Martínez-Díaz, J. A., Hernández‐Aguilar, M. E., Herrera‐Covarrubias, D., Rojas-Durán, F., Chi-Castañeda, D., García, L. I., & Aranda-Abreu, G. E. (2024) · Molecular Neurobiology · doi:10.1007/s12035-023-03908-5 · Cited by 11
Rasmussen, J., Ewing, A. D., Bodea, L., Bodea, G. O., Gearing, M., & Faulkner, G. J. (2021) · Brain Pathology · doi:10.1111/bpa.13018 · Cited by 10
Proteome-Scale Mapping of Perturbed Proteostasis in Living CellsPreprint
Lam, I., Hallacli, E., & Khurana, V. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a034124 · Cited by 9
“For instance, recent elegant work has connected genomic instability, chromatin relaxation, and the aberrant activation of transposable genetic elements in tauopathy, providing entirely new perspectives on how age-related cellular changes might amplify the toxic effects of misfolded proteins (Guo et al. 2018; Sun et al…”
BackgroundHuman 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
Sultana, O. F., Bandaru, M., Bushra, M. A., Reddy, P. H., & Reddy, A. P. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102957 · Cited by 11
Liu, X., Bienkowska, J. R., & Zhong, W. (2020) · PLoS ONE · doi:10.1371/journal.pone.0232994 · Cited by 10
Cappucci, U., Casale, A. M., Proietti, M., Marinelli, F., Giuliani, L., & Piacentini, L. (2022) · Cells · doi:10.3390/cells11244036 · Cited by 11
Transposable Elements: Emerging Therapeutic Targets in Neurodegenerative Diseases
Singh, S., Borkar, M. R., & Bhatt, L. K. (2024) · Neurotoxicity Research · doi:10.1007/s12640-024-00688-1 · Cited by 11
“Furthermore, the overexpression of Tau has been demonstrated to hinder the post-transcriptional suppression of TEs in the brains of flies by reducing the expression of PIWI proteins (Sun et al. 2018).”
InfluentialSuyama, R., & Kai, T. (2024) · FEBS Journal · doi:10.1111/febs.17360 · Cited by 10
“Furthermore, several TEs are upregulated in a Drosophila model of tauopathy expressing pathogenic Tau, where overexpression of Piwi suppresses dysregulated TEs in the brain [188].”
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-citationBukhari, H., Nithianandam, V., Battaglia, R. A., Cicalo, A., Sarkar, S., Comjean, A., Hu, Y., Leventhal, M. J., Dong, X., & Feany, M. Β. (2024) · Genome Research · doi:10.1101/gr.278576.123 · Cited by 11
“In Figure 2”
InfluentialHuman endogenous retroviruses in viral disease and therapy
Li, Y., Fan, T.-J., & Cui, J. (2022) · Clinical and Translational Discovery · doi:10.1002/ctd2.38 · Cited by 8
New approaches for understanding the potential role of microbes in Alzheimer's disease
Whitson, H. E., Banks, W. A., Diaz, M. M., Frost, B. E., Kellis, M., Lathe, R., Schmader, K. E., Spudich, S., Tanzi, R. E., & Garden, G. A. (2024) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2024.100743 · Cited by 8
“Retro-transposons, particularly endogenous retroviruses, are activated at the RNA level across Drosophila, mouse, and human tauopathy, including AD (W. Sun et al., 2018; Guo et al., 2018; Ramirez et al., 2022; Wahl et al., 2023).”
BackgroundInfluentialSelf-citationInvolvement of transposable elements in Alzheimer’s disease pathogenesis
Mustafin, R. N., & Хуснутдинова, Э. К. (2024) · Vavilov Journal of Genetics and Breeding · doi:10.18699/vjgb-24-27 · Cited by 8
“A significant increase in HERVs transcripts was also found in AD brains (Sun et al., 2018).”
BackgroundLooking at Alzheimer’s Disease Pathogenesis from the Nuclear Side
D’Andrea, L., Stringhi, R., Luca, M. D., & Marcello, E. E. (2021) · Biomolecules · doi:10.3390/biom11091261 · Cited by 8
Zhu, Z., Li, Y., Liang, M., et al. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00190 · Cited by 8
The Biological Intersection Between Chemotherapy-Related Cognitive Impairment and Alzheimer Disease
Torre, M., Zanella, C. A., & Feany, M. Β. (2025) · American Journal Of Pathology · doi:10.1016/j.ajpath.2024.12.013 · Cited by 8
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
“…expression of endogenous retroviral mRNA and proteins has been observed in protein aggregation diseases (Ezzat et al., 2019; Douville et al., 2011; Sun et al., 2018; Ochoa et al., 2023; Frost and Dubnau, 2024; Schneider et al., 2024), for example in tau pathologies (Sun et al., 2018), such as…”
The potential of piR-823 as a diagnostic biomarker in oncology: A systematic review
Sohn, E. J., Han, M., Park, Y. M., Kim, Y. H., & Oh, S. (2023) · PLoS ONE · doi:10.1371/journal.pone.0294685 · Cited by 8
Pathogenic Microglia Orchestrate Neurotoxic Properties of Eomes-Expressing Helper T Cells
Zhang, C., Raveney, B. J. E., Takahashi, F., Yeh, T.-W., Hohjoh, H., Yamamura, T., & Oki, S. (2023) · Cells · doi:10.3390/cells12060868 · Cited by 10
piRNAs and endo-siRNAs: Small molecules with large roles in the nervous system
Ow, M. C., & Hall, S. E. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.105086 · Cited by 9
Human Endogenous Retrovirus Expression is Dynamically Regulated in Parkinson’s DiseasePreprint
Gordevičius, J., Goralski, T. M., Bergsma, A. L., Parham, A., Kuhn, E., Meyerdirk, L. K., McDonald, M., Milčiūtė, M., van Putten, E. I., Marshall, L. L., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.03.565438 · Cited by 9
Noncoding RNAs are indispensable architects and regulators of biomolecular condensates
Chen, S., Wang, C., Hu, J., Luo, T., Li, Q., & Shen, H. (2026) · Non-coding RNA Research · doi:10.1016/j.ncrna.2026.01.003 · Cited by 6
“Transposable element RNAs, usually kept suppressed by piRNAs and other pathways, are aberrantly expressed in some neurodegenerative diseases, and these RNAs might engage LLPS pathways or trigger innate immune responses via condensates [111].”
Selective neuronal vulnerability to deficits in RNA processing
Zuniga, G., & Frost, B. E. (2023) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2023.102500 · Cited by 8
Self-citationLombardo, S. D., Wangsaputra, I., Menche, J., & Stevens, A. (2022) · Genes · doi:10.3390/genes13050764 · Cited by 7
“However, despite their unpredictable jumps across the genome that may interrupt gene sequence and cause shifting mutations, certain diseases have shown specific associations with transposons, such as haemophilia [125] and Alzheimer’s disease [126].”
BackgroundValdebenito‐Maturana, B., Rojas-Tapia, M. I., Carrasco, M. A., & Tapia, J. C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232416222 · Cited by 8
“In Tau-associated pathologies, such as supranuclear palsy and Alzheimer’s disease (AD), TEs can become activated [14,15].”
BackgroundChennakesavan, K., Haorah, J., & Samikkannu, T. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102473 · Cited by 5
“95 Thus, recent studies indicated that targeting changes in piRNA levels could offer potential biomarkers for and a therapeutic approach to AD management.”
D’Ignazio, L., Lorenzetti, A. P. R., Penney, E. B., Evans, T. A., Qamar, B., McCord, A. E., Feltrin, A. S., Barbosa, A. R., Sheehan, B. J., Araújo, B. H. S., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115812 · Cited by 6
Epigenetic dysregulation of transposable elements in cognitive impairment and Alzheimer’s disease
Cavalier, A. N., Smith, M., McWilliams, G. T., McEntee, C. M., Bettcher, B. M., Coughlan, C. M., & LaRocca, T. J. (2025) · GeroScience · doi:10.1007/s11357-025-01765-9 · Cited by 7
Mustafin, R. N. (2024) · Vavilov Journal of Genetics and Breeding · doi:10.18699/vjgb-24-54 · Cited by 5
Mycobacterium paratuberculosis: A HERV Turn-On for Autoimmunity, Neurodegeneration, and Cancer?
Dow, C. T., Pierce, E. S., & Sechi, L. A. (2024) · Microorganisms · doi:10.3390/microorganisms12091890 · Cited by 10
“HERVs have been implicated in the pathogenesis of AD [136,137].”
BackgroundRetrotransposon SINEs in age-related diseases: Mechanisms and therapeutic implications
Shah, S., Yu, S., Zhang, C., Ali, I., Wang, X., Qian, Y., & Xiao, T. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102539 · Cited by 5
Beatini, S., Rosa, L. L., Giantomasi, L., & Tonelli, D. D. P. (2025) · Brain Organoid and Systems Neuroscience Journal · doi:10.1016/j.bosn.2025.06.003 · Cited by 4
Brain somatic mutations in Alzheimer’s disease: linking genetic mosaicism to neurodegeneration
Li, Z., Zhang, J., Liu, Z., Yu, L., Yang, C., Zhang, L., Xiang, Z., Hu, F., Brazh, N., Shu, K., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00895-0 · Cited by 6
“Aging fruit flies exhibit increased transposon activity [255, 256], but the evidence in AD remains mixed: while some studies found no significant increase in L1 activity [257], others reported upregulated expression of transposable elements, including L1 [186, 188].”
Korada, S., Tam, O. H., Greco, H. C., Hammell, M., Dubnau, J., & Sher, R. B. (2025) · PLoS Genetics · doi:10.1371/journal.pgen.1012007 · Cited by 6
Wahl, D., Grant, R. A., & LaRocca, T. J. (2024) · Experimental Gerontology · doi:10.1016/j.exger.2024.112458 · Cited by 4
“3TC has also been reported to prevent tau-associated neuronal death in transgenic Drosophila models (Sun et al., 2018) and attenuate tau phosphorylation, inflammation, neuronal pruning and hippocampal atrophy in P301S mice (a model of tau overexpression) (Vall ´ es-Saiz et al., 2023).”
BackgroundProceedings of the inaugural Dark Genome Symposium: November 2022
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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
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“De-repression/ overexpression of retrotransposons in adult neurons of Drosophila models of neurodegenerative disease canalso leadto cell death 54,55 .”
RNA Modifications in Neurodegenerations
Calzoni, E., Argentati, C., Cesaretti, A., Montegiove, N., Tortorella, I., Bazzucchi, M., Morena, F., Martino, S., & Emiliani, C. (2021) · RNA technologies · doi:10.1007/978-3-030-71612-7_2 · Cited by 5
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Silva, G. M., Picone, J. A., Kaplan, A. L., Park, C. R., Lira, D. P., Kim, R. K., Truby, N. L., Neve, R. L., Cui, X., & Hamilton, P. J. (2025) · Biological Psychiatry · doi:10.1016/j.biopsych.2025.07.014 · Cited by 4
Mechanisms and targeted treatments of cobalt-encephalopathy from cobalt-chromium orthopedic implants
Wu, T., Li, H., & Chen, W. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.08.008 · Cited by 3
Maxwell, H., Smith, J. C., Campbell, T., Clark, J., Rocca, R. L., Paonessa, F., Sitnikov, S., Evans, M. L., Maycox, P. R., & Livesey, F. J. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70620 · Cited by 3
“11 All of these phenotypes are considered pathogenic in nature, potentially through derepression of neuronal heterochromatin and widespread genomic disruption.”
Metadata
- Authors
- Sun, W., Samimi, H., Gamez, M., Zare, H., & Frost, B.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Texas State University (US)
- Corresponding author
- Frost, Bess
- Venue
- Nature Neuroscience
- Published
- 2018-07-23
- Volume
- 21
- Issue
- 8
- Pages
- 1038-1048
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC6095477
- OpenAlex
- W2884899270
- Cited by
- 300
- References
- 68
- Citations by year
- 2026: 26 · 2025: 47 · 2024: 47 · 2023: 40 · 2022: 39 · 2021: 39 · 2020: 34 · 2019: 23 · 2018: 4
- FWCI
- 10.76
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Mayo Clinic
- Mayo Foundation for Medical Education and Research
- CurePSP
- University of Texas at Austin
- York University
- National Institute on Aging (R01AG018023, U01AG006786, P01AG003949, R01AG057896, P50AG025711, R01AG032990, P01AG017216, U01AG046139, P50AG016574)
- National Institute of Neurological Disorders and Stroke (R00NS088429, R01NS080820)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- tauopathy, transposable elements, Piwi, neuronal cell death, neurodegeneration, endogenous retroviruses, Alzheimer's disease, progressive supranuclear palsy, Drosophila melanogaster, epigenetic silencing
- MeSH terms
- Alzheimer Disease, Animals, DNA Transposable Elements, Drosophila melanogaster, Gene Expression Regulation, Humans, Motor Activity, Neurons, Supranuclear Palsy, Progressive, tau Proteins, Cell Death, Heredodegenerative Disorders, Nervous System, Tauopathies, Caloric Restriction, RNA, Small Interfering
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-20, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-20 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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