The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index; 12 of the 26 sources its claims cite were checked for support.
Tau promotes neurodegeneration through global chromatin relaxation
Open accessAbstract
The microtubule-associated protein tau is involved in a number of neurodegenerative disorders, including Alzheimer's disease. Previous studies have linked oxidative stress and subsequent DNA damage to neuronal death in Alzheimer's disease and related tauopathies. Given that DNA damage can substantially alter chromatin structure, we examined epigenetic changes in tau-induced neurodegeneration. We found widespread loss of heterochromatin in tau transgenic Drosophila and mice and in human Alzheimer's disease. Notably, genetic rescue of tau-induced heterochromatin loss substantially reduced neurodegeneration in Drosophila. We identified oxidative stress and subsequent DNA damage as a mechanistic link between transgenic tau expression and heterochromatin relaxation, and found that heterochromatin loss permitted aberrant gene expression in tauopathies. Furthermore, large-scale analyses from the brains of individuals with Alzheimer's disease revealed a widespread transcriptional increase in genes that were heterochromatically silenced in controls. Our results establish heterochromatin loss as a toxic effector of tau-induced neurodegeneration and identify chromatin structure as a potential therapeutic target in Alzheimer's disease.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
61 Own result · 33 Own interpretation · 15 Own method · 5 No full text of the sources · 4 Partly supported · 3 Supported · 3 No basis given · 2 Supported so far · 2 Sources not found · accuracy not yet measured
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
“These reporters were silenced in controls, but were expressed in tau transgenic Drosophila brains (Fig. 1e).”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Tau transgenic Drosophila have widespread alterations in chromatin structure
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A 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 total levels of H3K9me2 and HP1α were significantly decreased in tau transgenic Drosophila heads compared to controls (Fig. 1a, b).”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Tau transgenic Drosophila have widespread alterations in chromatin structure
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A 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
“Transgenic expression of tauWT or tauE14 also activated reporter expression in Drosophila (Supplementary Fig. 1e).”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Tau transgenic Drosophila have widespread alterations in chromatin structure
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.
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
“Neuronal expression of tauWT or tauE14 reduced H3K9me2 and HP1α levels (Supplementary Fig. 1b, c)”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Tau transgenic Drosophila have widespread alterations in chromatin structure
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.
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
“The extent of heterochromatin loss caused by expression of wild type or pseudohyperphosphorylated tau correlated with their respective toxicities.”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Tau transgenic Drosophila have widespread alterations in chromatin structure
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A 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
“Total H3K9me2 and HP1α levels (Fig. 2a, b, Supplementary Fig. 1f, g) and H3K9me2 and HP1α chromocenter labeling (Fig. 2c) were significantly increased in tau transgenic flies harboring a loss of function mutation in ash1 or RNAi targeted to NURF301.”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Genetic manipulation of chromatin structure modifies tau neurotoxicity
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 increased activation of the heterochromatin-embedded reporter in the brain (Fig. 3g, h)”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Oxidative stress promotes DNA damage and heterochromatin loss
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.
In the paper
“70% of β–galactosidase positive foci were positive for cleaved PARP, a marker of caspase activation21 (Fig. 1g).”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Tau transgenic Drosophila have widespread alterations in chromatin structure
What the sources say
- Not checked — no full text of the sourcecites [21] Williams, D.W., Kondo, S., Krzyzanowska, A., Hiromi, Y. & Truman, J.W. Local caspase activity directs engulfment of dendrites during pruning. Nat. Neurosci. 9, 1234–1236 (2006). source
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.
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
“Importantly, mutant Su(var)3-9 and Su(var)205 transgenes were not toxic in the absence of tau.”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Genetic manipulation of chromatin structure modifies tau neurotoxicity
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.
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 tauopathy mice, however, ring-like perinucleolar chromocenter staining was significantly reduced for both H3K9me2 and HP1α (Fig. 5a-c)”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Heterochromatin loss in vertebrate tauopathies
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. 19
- Probably not a substantial claim. 25
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Pan-neuronal transgenic expression of an FTDP-17 mutant form of human tau, tauR406W, in Drosophila causes progressive neurodegeneration and provides a well-characterized in vivo genetic model of tau neurotoxicity7,15,16.”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Tau transgenic Drosophila have widespread alterations in chromatin structure
What the sources say
- Partly supportedcites [7] Khurana, V. et al. TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model. Curr. Biol. 16, 230–241 (2006). sourceExperimental — accuracy not yet measured
The Introduction describes transgenic human or mutant tau expression in Drosophila as recapitulating progressive neurodegeneration, and the Results document age-dependent degeneration in tau-expressing flies. The methods identify a panneural expression driver. Our copy does not identify the flies showing these findings as expressing tauR406W, however; the Results explicitly name tauV337M for one genetic experiment. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [15] Wittmann, C.W. et al. Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science 293, 711–714 (2001). source
- Supportedcites [16] 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 panneuronal expression of human tau R406W in transgenic Drosophila as an in vivo model for studying tau-induced neurodegeneration. The section on oxidative stress and neurotoxicity reports that tau R406W expression produces progressive neurodegeneration in the fly brain. (LLM, conf=0.91)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“components of the piRNA pathway are associated with stem cell self-renewal and are aberrantly expressed in several types of somatic tumors50”
§ Tau promotes neurodegeneration through global chromatin relaxation > DISCUSSION
What the sources say
- Supportedcites [50] Juliano, C., Wang, J. & Lin, H. Uniting germline and stem cells: the function of Piwi proteins and the piRNA pathway in diverse organisms. Annu. Rev. Genet. 45, 447–469 (2011). source
The Conclusion (page not available in our copy) says the Piwi/piRNA pathway is required for maintaining germline stem cells. “The impact of Piwi proteins on human health” (page not available) reports that ectopic expression of the Piwi proteins hiwi or hili correlates with several cancer types, including breast, gastric, and ovarian cancers and soft tissue sarcomas. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. 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
“Indeed, increased expression of a regulatory RNA has already been implicated in the pathogenesis of AD49.”
§ Tau promotes neurodegeneration through global chromatin relaxation > DISCUSSION
What the sources say
- Supportedcites [49] Faghihi, M.A. et al. Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase. Nat. Med. 14, 723–730 (2008). source
The Results report elevated BACE1-AS, a regulatory noncoding RNA, in brain samples from people with Alzheimer’s disease compared with controls. The Discussion proposes that this elevation contributes to a feed-forward cycle of disease progression, supporting the claim’s cautious wording, “implicated.” (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The 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
“and is thought to protect DNA from oxidative damage46-48”
§ Tau promotes neurodegeneration through global chromatin relaxation > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [46] Krylova, S.M. et al. Tau protein binds single-stranded DNA sequence specifically—the proof obtained in vitro with non-equilibrium capillary electrophoresis of equilibrium mixtures. FEBS Lett. 579, 1371–1375 (2005). source
- Not checked — no full text of the sourcecites [47] Sjöberg, M.K., Shestakova, E., Mansuroglu, Z., Maccioni, R.B. & Bonnefoy, E. Tau protein binds to pericentromeric DNA: a putative role for nuclear tau in nucleolar organization. J. Cell Sci. 119, 2025–2034 (2006). source
- Supportedcites [48] Wei, Y. et al. Binding to the minor groove of the double-strand, tau protein prevents DNA from damage by peroxidation. PLoS ONE 3, e2600 (2008). source
The Results section reports that tau reduced hydroxyl-radical damage to DNA in vitro. The Discussion says this suggests tau protects DNA by blocking hydroxyl-radical attack, while noting that protection in vivo remains untested. (LLM, conf=0.92)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“No statistical methods were used to predetermine sample sizes but our sample sizes are similar to those reported in previous publications 7,16,44.”
§ Tau promotes neurodegeneration through global chromatin relaxation > ONLINE METHODS > Statistical Analysis
What the sources say
- Supportedcites [7] Khurana, V. et al. TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model. Curr. Biol. 16, 230–241 (2006). source
The citation points to a previous publication as a sample-size example, not as evidence about how the citing authors chose their own sample sizes. The cited paper’s experimental procedures (indexed as Discussion; page unavailable) report at least four brains per genotype for PCNA quantification and at least eight hemibrains per time point and genotype for TUNEL staining. (LLM, conf=0.85)
- Supportedcites [16] 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 citation identifies a previous publication with reported sample sizes. In “Histology, immunostaining, and TUNEL analysis,” the source says each graphed data point averaged counts from at least eight hemibrains. The statement about not using statistical methods to predetermine sample sizes describes the citing authors’ own study, not this source. (LLM, conf=0.86)
- Could not verifycites [44] DuBoff, B., Gotz, J. & Feany, M.B. Tau promotes neurodegeneration via DRP1 mislocalization in vivo. Neuron 75, 618–632 (2012). sourceExperimental — accuracy not yet measured
The Experimental Procedures (Immunoblotting; page unavailable) say immunoblots were repeated at least three times, but give no basis for comparing this paper’s sample sizes with those of the citing study. Searches for sample-size planning, sample counts, and comparisons with previous publications found no passage addressing that comparison. The statement about not predetermining sample sizes describes the citing authors’ own methods, not a claim this source can establish. (LLM, conf=0.70)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“EIFA4 and CYC1 were selected as internal controls for human RT-PCR based upon their stability in postmortem brain of AD patients54.”
§ Tau promotes neurodegeneration through global chromatin relaxation > ONLINE METHODS > Quantitative PCR
What the sources say
- Partly supportedcites [54] Penna, I. et al. Selection of candidate housekeeping genes for normalization in human postmortem brain samples. Int. J. Mol. Sci. 12, 5461–5470 (2011). sourceExperimental — accuracy not yet measured
The Results identify CYC1 as a stable reference gene in postmortem brain samples from AD patients and controls. The Discussion recommends CYC1 together with EIF4A2 for RT-qPCR normalization, but the claim names EIFA4 instead of EIF4A2. (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.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Pathologic tau causes an increase in actin stabilization18 that inhibits association of the fission protein Drp1 with mitochondria, leading to mitochondrial elongation and the production of reactive oxygen species44.”
§ Tau promotes neurodegeneration through global chromatin relaxation > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [18] Fulga, T.A. et al. Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo. Nat. Cell Biol. 9, 139–148 (2007). source
- Supportedcites [44] DuBoff, B., Gotz, J. & Feany, M.B. Tau promotes neurodegeneration via DRP1 mislocalization in vivo. Neuron 75, 618–632 (2012). source
The Discussion describes tau-mediated actin stabilization as mislocalizing DRP1 and producing mitochondrial elongation. It also reports excess ROS in tau flies with elongated mitochondria; the Results section ‘Reversing actin stabilization rescues tau-induced mitochondrial defects’ reports that reversing actin stabilization decreases ROS in tau transgenic neurons. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In vitro and in cultured cells, tau binds the minor groove of the DNA double helix”
§ Tau promotes neurodegeneration through global chromatin relaxation > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [46] Krylova, S.M. et al. Tau protein binds single-stranded DNA sequence specifically—the proof obtained in vitro with non-equilibrium capillary electrophoresis of equilibrium mixtures. FEBS Lett. 579, 1371–1375 (2005). source
- Not checked — no full text of the sourcecites [47] Sjöberg, M.K., Shestakova, E., Mansuroglu, Z., Maccioni, R.B. & Bonnefoy, E. Tau protein binds to pericentromeric DNA: a putative role for nuclear tau in nucleolar organization. J. Cell Sci. 119, 2025–2034 (2006). source
- Partly supportedcites [48] Wei, Y. et al. Binding to the minor groove of the double-strand, tau protein prevents DNA from damage by peroxidation. PLoS ONE 3, e2600 (2008). sourceExperimental — accuracy not yet measured
The Discussion reports that tau binds the minor groove of double-stranded DNA, supported by competition assays described in the Results. The Introduction reports tau in cell nuclei and prior evidence of nuclear DNA binding, but the paper does not establish minor-groove binding in cultured cells. No page numbers are available in our copy. (LLM, conf=0.87)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Every source the paper cites for this claim was checked and supports it.
In the paper
“To identify specific genes with reduced H3K9me2 levels, we performed H3K9me2-based ChIP-sequencing (ChIP-seq) in biological duplicate (Fig. 4a, http://genome.ucsc.edu30), and validated significantly H3K9me2 depleted genes with quantitative PCR (qPCR) (Fig. 4b).”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Heterochromatin loss permits aberrant gene expression in tau transgenic Drosophila
What the sources say
- Supportedcites [30] Kent, W.J. et al. The human genome browser at UCSC. Genome Res. 12, 996–1006 (2002). source
The citation is attached to the genome.ucsc.edu link in the citing sentence, identifying the UCSC Genome Browser rather than attributing the ChIP-seq experiment or qPCR validation to this paper. The paper’s “Using the Browser” section describes displaying genomic annotations as tracks, so it supports that identification. (LLM, conf=0.90)
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.
Probably not a substantial claim. It may state two separate claims as one.
- Supported
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
“Tau transgenic Drosophila, however, had significantly reduced chromocenter labeling, and instead had diffusely distributed H3K9me2 and HP1α (Fig. 1c, d, Supplementary Fig. 1d).”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Tau transgenic Drosophila have widespread alterations in chromatin structure
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
“Furthermore, loss of ash1 function or RNAi-mediated reduction of NURF301 significantly silenced expression of the heterochromatin-embedded reporter in tau transgenic flies (Fig. 2d).”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Genetic manipulation of chromatin structure modifies tau neurotoxicity
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: 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
“While PIWIL1 levels were very low in control mice, we observed approximately double the levels of PIWIL1 staining in motor neurons of tau transgenic mice (Fig. 5d).”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Heterochromatin loss in vertebrate tauopathies
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
“In pyramidal hippocampal neurons from postmortem control brains, H3K9me2 was concentrated in perinucleolar chromocenters. In AD, however, H3K9me2 staining was diffuse (Fig. 6a)”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Heterochromatin loss in vertebrate tauopathies
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
“RNAi transgenes targeted to ash1, NURF301, and NURF38 were not toxic in the absence of tau, nor was loss of ash1 function.”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Genetic manipulation of chromatin structure modifies tau neurotoxicity
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
“and PCNA positive foci (Fig. 2m) compared to tau expressed alone.”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Genetic manipulation of chromatin structure modifies tau neurotoxicity
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.
The quote only partly states this claim.
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
“Transgenic RNAi targeted to Ago3 did not affect levels of transgenic tau or tau phosphorylation (Supplementary Fig. 2b)”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Heterochromatin loss permits aberrant gene expression in tau transgenic 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
“Ago3/PIWIL1 was overexpressed in tau transgenic Drosophila and mice, and in human AD.”
§ Tau promotes neurodegeneration through global chromatin relaxation > DISCUSSION
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
“There were eleven genes that were identified as significant in both experiments”
§ Tau promotes neurodegeneration through global chromatin relaxation > ONLINE METHODS > ChIP-seq Analysis
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
“For the first experiment, we found 2,456 significant regions covering 167 different genes, and for the biological replicate we found 143 significant regions covering 22 different genes.”
§ Tau promotes neurodegeneration through global chromatin relaxation > ONLINE METHODS > ChIP-seq Analysis
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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Similar results were obtained with both internal controls.”
§ Tau promotes neurodegeneration through global chromatin relaxation > ONLINE METHODS > Quantitative PCR
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 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
“Together, these findings suggest that tau-induced heterochromatin loss permits aberrant gene expression that is coincident with tau neurotoxicity, cell cycle reentry, and subsequent apoptosis of postmitotic neurons.”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Tau transgenic Drosophila have widespread alterations in chromatin structure
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“confirming that these genetic manipulations damage DNA (Fig. 3c, d).”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Oxidative stress promotes DNA damage and heterochromatin loss
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These tau transgenic mice undergo progressive neurodegeneration, and develop neurofibrillary tangles in the brain and spinal cord35.”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Heterochromatin loss in vertebrate tauopathies
What the sources say
- Not checked — no full text of the sourcecites [35] Lewis, J. et al. Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat. Genet. 25, 402–405 (2000). source
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 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
“suggesting that dysregulation of the piRNA pathway leads to loss of proliferative control”
§ Tau promotes neurodegeneration through global chromatin relaxation > DISCUSSION
hedgeddirect- 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
“Experiments were carried out in biological duplicates.”
§ Tau promotes neurodegeneration through global chromatin relaxation > ONLINE METHODS > ChIP-seq Analysis
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
“Each data point is the result of at least three biological replicates each composed of three technical replicates.”
§ Tau promotes neurodegeneration through global chromatin relaxation > ONLINE METHODS > Quantitative PCR
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 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
“We have found that oxidative stress causes DNA damage, heterochromatin loss and consequent aberrant gene expression in Drosophila.”
§ Tau promotes neurodegeneration through global chromatin relaxation > 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 claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Ago3 regulates PIWI-interacting RNAs, or piRNAs, a large class of highly conserved small noncoding RNAs that are responsible for silencing transposons33,34.”
§ Tau promotes neurodegeneration through global chromatin relaxation > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [33] Aravin, A. et al. A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442, 203–207 (2006). source
- Not checked — no full text of the sourcecites [34] Girard, A., Sachidanandam, R., Hannon, G.J. & Carmell, M.A. A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 442, 199–202 (2006). 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.
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
“Data were collected and processed side by side in randomized order for all experiments.”
§ Tau promotes neurodegeneration through global chromatin relaxation > ONLINE METHODS > Statistical Analysis
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
“For experiments in mice and human tissue, sample sizes were based on power analysis calculations, which demonstrated that a 30% difference between 6 cases and controls will achieve a power of 80%.”
§ Tau promotes neurodegeneration through global chromatin relaxation > ONLINE METHODS > Statistical Analysis
boostedn = 6- 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 cultured rat embryonic fibroblasts and in the adult rat liver, metabolic stress induced by caloric restriction increases Suv39h1, the mammalian homolog of Su(var)3-945.”
§ Tau promotes neurodegeneration through global chromatin relaxation > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [45] Bosch-Presegué, L. et al. Stabilization of Suv39H1 by SirT1 is part of oxidative stress response and ensures genome protection. Mol. Cell 42, 210–223 (2011). 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.
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
“heterochromatin loss likely permits increased expression of non-protein coding RNA transcripts”
§ Tau promotes neurodegeneration through global chromatin relaxation > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“We used RT-PCR to confirm RNAi-mediated knockdown of Su(var)205 and Su(var)3-9 (Supplementary Fig. 2a).”
§ Tau promotes neurodegeneration through global chromatin relaxation > RESULTS > Oxidative stress promotes DNA damage and heterochromatin loss
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our data suggest that DNA-damage induced heterochromatin loss causes a global shift in gene expression towards a more developmental state that results from neuronal dedifferentiation, triggering inappropriate cell cycle reentry and subsequent apoptosis”
§ Tau promotes neurodegeneration through global chromatin relaxation > DISCUSSION
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.
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
“Data collection and analysis were not routinely performed blind to the conditions of the experiments.”
§ Tau promotes neurodegeneration through global chromatin relaxation > ONLINE METHODS > Statistical Analysis
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
“JNPL3 mice are housed 2-5 per cage in a vivarium with a 12 hour off/on light/dark cycle and are used compliance with ethical guidelines and regulations.”
§ Tau promotes neurodegeneration through global chromatin relaxation > ONLINE METHODS > Genetics and Animal Models
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
“This non-parametric test is the most appropriate to use when the underlying distribution is unknown and the sample size is small.”
§ Tau promotes neurodegeneration through global chromatin relaxation > ONLINE METHODS > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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
“human control and AD brains with a postmortem interval of less than 24 hours were collected through the autopsy service at Brigham and Women’s Hospital under the appropriate IRB.”
§ Tau promotes neurodegeneration through global chromatin relaxation > ONLINE METHODS > Human brain analyses
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.
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
“This procedure ensures that the input is minimally informative about the normalized ChIP.”
§ Tau promotes neurodegeneration through global chromatin relaxation > ONLINE METHODS > ChIP-seq Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check 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. It may be too vague to check against evidence. 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
“We tested for independence between both expression and chromatin states with a large sample size, and thus fulfilled the criteria for this non-parametric test.”
§ Tau promotes neurodegeneration through global chromatin relaxation > ONLINE METHODS > Statistical Analysis
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.
The paper relies on this without support.
The human AD postmortem brain samples and controls are representative of AD and non-demented controls, respectively, and differ only in AD-related pathology.
“We next used quantitative methods to validate the loss of H3K9me2 and increase of PIWIL1 levels in AD in age-, gender-, and postmortem interval-matched cases and controls.”
The paper relies on this without support.
The fetal brain gene expression profile is a valid reference for a dedifferentiated state.
“We compared gene expression profiles of fetal brains, human control hippocampal neurons, hippocampal neurons from AD, and whole hippocampal tissue from control and three stages of AD.”
The paper relies on this without support.
Ago3 is homologous to the human gene PIWIL1.
“Ago3 is homologous to the human gene PIWIL1”
The paper relies on this without support.
CG15661 is homologous to the human gene UGT1A10.
“CG15661 is homologous to the human gene UGT1A10.”
The paper relies on this without support.
Variance is similar between groups that are being compared.
“Variance is similar between groups that are being compared.”
The authors state this as an assumption.
Data distribution is normal (except for ChIP-seq analysis).
“Data distribution was assumed to be normal but this was not formally tested except for ChIP-seq analysis.”
The paper relies on this without support.
The simple external exoskeleton structure of the fly results in head preparations composed of primarily nervous system tissue.
“the simple external exoskeleton structure of the fly results in head preparations composed of primarily nervous system tissue.”
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
“Drosophila models of human tauopathy have progressive, age-associated neuronal death, a shortened lifespan, and decreased locomotor activity10,11.”
From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [10]
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
“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.”
From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [10]
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 Frost et al. 2014
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
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 [137]
The cited source says what the claim attributes to it.
In the citing paper
“We have previously identified tau-induced decondensation of constitutive heterochromatin as a key event that mediates neuronal death in tauopathy10.”
From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing 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.”
From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing 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.”
From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing 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.”
From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing 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.”
From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“Sample sizes are similar to or greater than those reported in previous publications4,5,10.”
From Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies (2018) · cites this paper as [10]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Self-check results appear here once an independent check has confirmed them.
Cited works that were retracted
Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.
A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
In the paper
“Ash1 is a histone methyltransferase that promotes euchromatin formation and transcriptional activation by methylating histones such as H3K4 and H3K36 22 .”
Cited work 10.1038/nature01126 · retracted 2015-05-07 · notice 10.1038/nature14421 · this paper published 2014-01-26
Citations
Cites
1 retracted
Histone methylation by the Drosophila epigenetic transcriptional regulator Ash1
Beisel, C., Imhof, A., Greene, J., Kremmer, E., & Sauer, F. (2002) · Nature · doi:10.1038/nature01126 · Cited by 310 · cited 2×
“Ash1 is a histone methyltransferase that promotes euchromatin formation and transcriptional activation by methylating histones such as H3K4 and H3K36 22 .”
RetractedUltrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849
The Human Genome Browser at UCSC
Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., & Haussler, A. D. (2002) · Genome Research · doi:10.1101/gr.229102 · Cited by 10,400
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498
Discrete Small RNA-Generating Loci as Master Regulators of Transposon Activity in Drosophila
Brennecke, J., Aravin, A. A., Stark, A., Dus, M., Kellis, M., Sachidanandam, R., & Hannon, G. J. (2007) · Cell · doi:10.1016/j.cell.2007.01.043 · Cited by 2,524 · cited 1×
“Ago3 regulates PIWI-associated RNAs (piRNAs) 32 , a highly conserved class of small RNAs that are required for post-transcriptional gene silencing of transposons 33,34 .”
Lee, V. M.-Y., Goedert, M., & Trojanowski, J. Q. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1121 · Cited by 2,480 · cited 1×
“A major pathological feature of AD and other tauopathies is the accumulation of abnormally phosphorylated forms of tau in the brains of affected individuals 1 .”
ChromHMM: automating chromatin-state discovery and characterization
Ernst, J., & Kellis, M. (2012) · Nature Methods · doi:10.1038/nmeth.1906 · Cited by 2,457
The NIH Roadmap Epigenomics Mapping Consortium
Bernstein, B. E., Stamatoyannopoulos, J. A., Costello, J. F., Ren, B., Milosavljevic, A., Meissner, A., Kellis, M., Marra, M. A., Beaudet, A. L., Ecker, J. R., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt1010-1045 · Cited by 1,892 · cited 1×
“In order to classify genes as heterochromatic or euchromatic, we utilized ChIP-seq data sets for all six publicly available histone modifications in the human hippocampus: H3K4me1, H3K4me3, H3K36me3, H3K9me3, H3K27me3, and H3K9ac (NIH Epigenomics Roadmap Project 37 ).”
A germline-specific class of small RNAs binds mammalian Piwi proteins
Girard, A., Sachidanandam, R., Hannon, G. J., & Carmell, M. A. (2006) · Nature · doi:10.1038/nature04917 · Cited by 1,762 · cited 2×
“Ago3 regulates PIWI-interacting RNAs, or piRNAs, a large class of highly conserved small noncoding RNAs that are responsible for silencing transposons 33,34 .”
Cited by
Sorted by citations
Roles of tau protein in health and disease
Guo, T., Noble, W., & Hanger, D. P. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1707-9 · Cited by 1,003
Chromatin-state discovery and genome annotation with ChromHMM
Ernst, J., & Kellis, M. (2017) · Nature Protocols · doi:10.1038/nprot.2017.124 · Cited by 905
“ChromHMM has had applications to studying diseases such as Alzheimer’s disease 28,29 , neurodegeneration 30 , type 2 diabetes 31 , and cancer 32–35 , among many other diseases.”
Arendt, T., Stieler, J. T., & Holzer, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.018 · Cited by 609
The road to restoring neural circuits for the treatment of Alzheimer's disease
Canter, R. G., Penney, J., & Tsai, L.-H. (2016) · Nature · doi:10.1038/nature20412 · Cited by 565
Tau association with synaptic vesicles causes presynaptic dysfunction
Zhou, L., McInnes, J., Wierda, K., Holt, M., Herrmann, A. G., Jackson, R. J., Wang, Y.-C., Swerts, J., Beyens, J., Miskiewicz, K., et al. (2017) · Nature Communications · doi:10.1038/ncomms15295 · Cited by 434
Metadata
- Authors
- Frost, B., Hemberg, M., Lewis, J., & Feany, M. B.
- Affiliations
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- University of Florida (US)
- Venue
- Nature Neuroscience
- Published
- 2014-01-26
- Volume
- 17
- Issue
- 3
- Pages
- 357-366
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4012297
- OpenAlex
- W2006588853
- Cited by
- 495
- References
- 61
- Citations by year
- 2026: 41 · 2025: 38 · 2024: 42 · 2023: 48 · 2022: 52 · 2021: 48 · 2020: 43 · 2019: 31 · 2018: 41 · 2017: 36 · 2016: 28 · 2015: 30 · 2014: 16
- FWCI
- 13.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institute on Aging (R01AG044113, R01AG033518, F32AG039193)
- National Cancer Institute (P01CA095616)
- National Institute of General Medical Sciences (R01GM084947)
- National Institute of Neurological Disorders and Stroke (U24NS050606, R21NS070250)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- tau protein, neurodegeneration, heterochromatin loss, chromatin relaxation, Alzheimer's disease, tauopathy, oxidative stress, DNA damage, epigenetic modifications, aberrant gene expression, therapeutic target
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Animals, Brain, Disease Models, Animal, Drosophila melanogaster, Female, Heterochromatin, Humans, Male, Mice, Inbred C57BL, Nerve Degeneration, tau Proteins, Tauopathies, Animals, Genetically Modified, Mice
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 ›
Are you an author, or do you see a problem with this page? Request a review
