The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index; 4 of the 6 sources its claims cite were checked for support.
Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease
Open accessAbstract
Histone deacetylase inhibitors (HDACIs) alter gene expression epigenetically by interfering with the normal functions of HDAC. Given their ability to decrease Aβ levels, HDACIs area potential treatment for Alzheimer's disease (AD). However, it is unclear how HDACIs alter Aβ levels. We developed two novel HDAC inhibitors with improved pharmacological properties, such as a longer half-life and greater penetration of the blood-brain barrier: mercaptoacetamide-based class II HDACI (coded as W2) and hydroxamide-based class I and IIHDACI (coded as I2) and investigated how they affect Aβ levels and cognition. HDACI W2 decreased Aβ40 and Aβ42 in vitro. HDACI I2 also decreased Aβ40, but not Aβ42. We systematically examined the molecular mechanisms by which HDACIs W2 and I2 can decrease Aβ levels. HDACI W2 decreased gene expression of γ-secretase components and increased the Aβ degradation enzyme Mmp2. Similarly, HDACI I2 decreased expression of β- and γ-secretase components and increased mRNA levels of Aβ degradation enzymes. HDACI W2 also significantly decreased Aβ levels and rescued learning and memory deficits in aged hAPP 3x Tg AD mice. Furthermore, we found that the novel HDACI W2 decreased tau phosphorylation at Thr181, an effect previously unknown for HDACIs. Collectively, these data suggest that class II HDACls may serve as a novel therapeutic strategy for AD.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Novel mercaptoacetamide-based class II HDAC inhibitor W2 lowers Aβ levels, reduces tau phosphorylation at Thr181, and improves learning and memory in hAPP 3xTg AD mice. The study also identifies transcriptional downregulation of Aβ-producing enzymes and upregulation of Aβ-degrading enzymes as possible mechanisms.
Key findings
- In N2a-APP cells, W2 decreased human Aβ40 and Aβ42 by 20%, while I2 significantly decreased Aβ40 but not Aβ42; W2 or I2 also decreased rodent Aβ40 by 20% in primary cortical neurons.
- W2 increased cell surface APP by 33% at 2 hrs and both W2 and I2 increased it about twofold at 24 hrs; in vivo, W2 increased sAPPα and decreased sAPPβ.
- In 9–10 month old hAPP 3xTg AD mice, W2 (50 mg/kg daily i.p.) decreased soluble Aβ40 after 2 weeks and decreased soluble and insoluble Aβ40 and Aβ42 after 4 weeks; W2 also reduced Thr181 phospho-tau by approximately 50% without changing total tau or tau kinases.
- W2 improved learning and memory in wild-type mice and rescued cognitive deficits in 9–10 month old hAPP 3xTg AD mice, as shown by increased platform crossings without altered swim speed.
Methods
- In vitro: N2a cells overexpressing hAPP, primary rat cortical and hippocampal neurons, Aβ ELISA, cell surface biotinylation, live cell surface staining, and qPCR for Aβ synthesis/degradation genes.
- In vivo: 9–10 month old hAPP 3xTg AD mice and 2–3 month old wild-type mice received W2 (50 mg/kg, daily i.p.) or control for 2 or 4 weeks; brain Aβ was measured by DEA/FA fractionation and ELISA, with immunoblotting for APP cleavage products and tau phosphorylation.
- Behavior: Morris water maze assessed spatial learning and memory; statistics used two-tailed t-tests or one-way ANOVA with Tukey’s post-hoc, and two-way ANOVA for escape latencies, with significance at p<0.05.
Limitations
- The paper states that the lowest optimal dose of HDACIs and additional molecular mechanisms affecting cognitive performance are still being investigated.
- Evident from the text: I2 was not tested in vivo; W2 was selected for in vivo work because it was more effective in reducing Aβ in vitro, so the in vivo findings apply only to W2.
- Evident from the text: the study reports cognitive rescue in the 3xTg AD model but does not establish whether the effects generalize to other AD models or to human AD.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
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Verification
Claims the paper makes
21 Own result · 10 Own interpretation · 2 Partly supported · 1 Couldn’t confirm · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Thus, APP located at the cell surface is more likely to undergo α-secretase cleavage to produce sAPPα, thereby reducing Aβ production.”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Class II HDACIs W2 and I2 decrease Aβ levels in vitro
What the sources say
- Partly supportedcites De Strooper, et al., 2010 sourceExperimental — accuracy not yet measured
The α-Secretases, Biological activity section says α-secretase cleavage produces soluble APPsα and can reduce Aβ production, although the latter finding has not been universally replicated. It does not say that APP at the cell surface is more likely to undergo this cleavage than APP elsewhere. (LLM, conf=0.86)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
A 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 observed a similar increase in surface levels of APP with HDACI W2 (n=3, Figs. 2E, F).”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Class II HDACIs W2 and I2 decrease Aβ levels in vitro
plaindirectn = 3- 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
“Since we observed a greater effect on Aβ levels by treating with HDACI W2 compared to I2in vitro, we continued to examine the effect of HDACI W2 on Aβ production in vivo.”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Class II HDACI W2 decreases Aβ levelsin hAPP 3xTg AD mice
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
“We found that W2 treatment improved learning and memory in 9-10 month old hAPP 3x Tg AD mice as evidenced by increased number of platform crossings without altering swim speed (Figs. 6E-H, n=12/group).”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Class II HDACI W2 improves learning and memory in hAPP 3x Tg AD mice
plaindirectn = 12- 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
“while I2 significantly repressed expression of β-(BACE1) and γ-secretase components (Nicastrin and Psen2) (Figs.3C, D).”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Transcriptional regulation of Aβ synthesis and degradation enzymes by HDACIs W2 and I2
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
“while HDACI I2 increased Nep, Ece1, Mmp2, Ctsd and Ctsb expression (Figs. 3E, F).”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Transcriptional regulation of Aβ synthesis and degradation enzymes by HDACIs W2 and I2
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
“Further experiments demonstrated that W2 significantly decreased mRNA levels of γ-secretase components (Psen1, Psen2, and Nicastrin)”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Transcriptional regulation of Aβ synthesis and degradation enzymes by HDACIs W2 and I2
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A 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
“Quantification of immunoblot results demonstrated that W2 (5 μM) significantly increased cell surface APP within 2 hrs (n=3; by 33 %, *P<0.05, Figs. 2A, B).”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Class II HDACIs W2 and I2 decrease Aβ levels in vitro
boosteddirectn = 3- 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 examined rodent Aβ levels in primary cortical neurons following HDACI treatment, and found that HDACI W2 or I2 significantly decreased rodent Aβ40 (by 20%, Figs. 1E, F; n=6-8).”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Class II HDACIs W2 and I2 decrease Aβ levels in vitro
plaindirectn = 6- 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
“However, W2 did not alter tau phosphorylation at the Thr231 site, other serine residues, or the total level of tau (Figs. 5D-F).”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Class II HDACI W2 decreases tau phosphorylation at Thr181 in hAPP 3xTg AD mice
plainn = 4- 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. 10
- Probably not a substantial claim. 1
- 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
“We developed two novel HDAC inhibitors with improved pharmacological properties, such as a longer half-life and greater penetration of the blood-brain barrier: mercaptoacetamide-based class II HDACI (coded as W2) and hydroxamide-based class I and IIHDACI (coded as I2)”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Abstract
What the sources say
- Partly supportedcites Konsoula and Jung, 2008 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites Konsoula, et al., 2009 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites Konsoula, et al., 2011 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.
It may state two separate claims as one.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Interestingly, several recent studies reported that the commercially available HDACIs alter Aβ levels by an unknown mechanism (Kilgore et al., 2010;Ricobaraza et al., 2011).”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Introduction
What the sources say
- Could not verifycites Kilgore et al., 2010 sourceExperimental — accuracy not yet measured
The Results and Discussion report that HDAC inhibitors restored memory performance in APP/PS1 mice, while the Discussion mentions elevated Aβ in the context of Alzheimer’s pathology. Neither those passages nor searches for treatment-related changes in amyloid levels show that the inhibitors altered Aβ levels or discuss a mechanism for such a change. (LLM, conf=0.73)
- Not matchedcites Ricobaraza et al., 2011
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: 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.
- 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
“HDACI W2 treatment significantly decreased soluble Aβ40 levels compared to control-injected mice, but there was no change in soluble Aβ42 levels (Figs.4A, B, n=10/group).”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Class II HDACI W2 decreases Aβ levelsin hAPP 3xTg AD mice
plaindirectn = 10- 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
“Additionally, we observed that HDACI W2 treatment significantly increased Mmp2 expression”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Transcriptional regulation of Aβ synthesis and degradation enzymes by HDACIs W2 and I2
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.
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
“We initially injected 2-3 month old wild-type mice for 4 weeks with W2 (50 mg/kg, daily i.p.) or control (10% DMSO), and found that W2 treated wild-type mice had improved learning and memory as evidenced by increased time spent in the target quadrant and number of platform crossings without altering swim speed (Figs. 6A-D, n=12/group).”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Class II HDACI W2 improves learning and memory in hAPP 3x Tg AD mice
plaindirectn = 12- 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
“Interestingly, HDACI W2 specifically reduced phosphorylation of tau at the Thr181 site (Figs. 5D-F, n=4).”
- Also stated in: § Class II HDACI W2 decreases tau phosphorylation at Thr181 in hAPP 3xTg AD mice · plain
“Quantification of these blots revealed that the HDACI W2 induced an approximately 50% decrease in levels of the Thr181 phospho-tau protein (Fig. 5F, n=4/group).”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Class II HDACI W2 decreases tau phosphorylation at Thr181 in hAPP 3xTg AD mice
plaindirectn = 4- 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: § Class II HDACI W2 decreases tau phosphorylation at Thr181 in hAPP 3xTg AD mice · plain
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
“Interestingly, 5 μM I2 significantly decreased human Aβ40 levels in N2a-APP cells; however, there were no changes in human Aβ42 levels compared to control (Figs. 1C,D; n=6).”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Class II HDACIs W2 and I2 decrease Aβ levels in vitro
plaindirectn = 6- 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
“HDACI W2 treatment significantly increased sAPPα and significantly decreased sAPPβ, compared to the control group (Figs.4E, F, n=3/group).”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Class II HDACI W2 decreases Aβ levelsin hAPP 3xTg AD mice
plaindirectn = 3- 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
“HDAC inhibition decreased expression of genes involved in Aβ production and induced expression of Aβ degradation enzymes.”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Conclusions
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.
- Rests on an assumption: HDAC inhibitors alter gene expression epigenetically by interfering with normal HDAC functions.
- Rests on an assumption: Changes in mRNA levels of Aβ synthesis and degradation enzymes lead to corresponding changes in enzyme activity and Aβ clearance.
- Rests on an assumption: W2 and I2 inhibit HDACs in the tested systems.
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 suggest that our novel compounds have dual effects of down-regulating Aβ production pathways while simultaneously up-regulating Aβ clearance mechanisms.”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Transcriptional regulation of Aβ synthesis and degradation enzymes by HDACIs W2 and I2
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: Changes in mRNA levels of Aβ synthesis and degradation enzymes lead to corresponding changes in enzyme activity and Aβ clearance.
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
“Collectively, these data suggest that our novel HDACI W2 not only affected Aβ levels, but also modulated tau phosphorylation at Thr181in vivo.”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Class II HDACI W2 decreases tau phosphorylation at Thr181 in hAPP 3xTg AD mice
hedgeddirectn = 4- 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
“Our study demonstrates that the novel Class II HDACI W2 decreases Aβ levelsand improves learning and memory.”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Conclusions
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.
The paper relies on this without support.
HDAC inhibitors alter gene expression epigenetically by interfering with normal HDAC functions.
“Histone deacetylase inhibitors (HDACIs) alter gene expression epigenetically by interfering with the normal functions of HDAC.”
The paper relies on this without support.
Commercially available HDACIs have poor pharmacological properties.
“However, these commercially available HDACIs have poor pharmacological properties.”
The paper relies on this without support.
9-10 month old hAPP 3xTg AD mice exhibit mild cognitive impairment.
“we injected 9-10 month old hAPP 3x Tg AD mice (with mild cognitive impairment) for 4 weeks with W2 (50 mg/kg, daily i.p.) or control.”
The paper relies on this without support.
Findings in mouse models of AD translate to therapeutic benefit in human dementias, including AD.
“Taken together, these data demonstrate that our novel compound Class II HDACI W2 mayhave the potential toalleviatecritical neuropathogenic processes in dementias, including AD, providing broad-spectrum therapeutic benefits.”
The paper relies on this without support.
Changes in mRNA levels of Aβ synthesis and degradation enzymes lead to corresponding changes in enzyme activity and Aβ clearance.
“Taken together, our data suggest that our novel compounds have dual effects of down-regulating Aβ production pathways while simultaneously up-regulating Aβ clearance mechanisms.”
The paper relies on this without support.
W2 and I2 inhibit HDACs in the tested systems.
“HDAC inhibition decreased expression of genes involved in Aβ production and induced expression of Aβ degradation enzymes.”
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
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Results > Class II HDACI W2 decreases tau phosphorylation at Thr181 in hAPP 3xTg AD mice
“However, it is unknown whether HDACIs can alter tau phosphorylation.”
§ Mercaptoacetamide-based class II HDAC inhibitor lowers Aβ levels and improves learning and memory in a mouse model of Alzheimer's disease > Discussion
“Interestingly, the HDACI nicotinamide increases the level of acetylated α-tubulin, and selectively decreases Thr231-phosphotau in 3x-Tg AD mice (Green, et al., 2008, Hempen and Brion, 1996).”
Citations
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Temporal Profile of Amyloid-β (Aβ) Oligomerization in an in Vivo Model of Alzheimer Disease
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Oxidative Stress in Cognitive and Epigenetic Aging: A Retrospective Glance
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Metadata
- Authors
- Sung, Y. M., Lee, T., Yoon, H., DiBattista, A. M., Song, J. M., Sohn, Y., Moffat, E. I., Turner, R. S., Jung, M., Kim, J., & Hoe, H.-S.
- Affiliations
- Seoul National University (KR)
- Georgetown University Medical Center (US)
- Washington University in St. Louis (US)
- Corresponding author
- Kim, Jungsu
- Hoe, Hyang-Sook
- ORCID
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 239
- Pages
- 192-201
- ISSN
- 0014-4886 (ISSN-L)
- PMC
- PMC3780389
- OpenAlex
- W2080228122
- Semantic Scholar
- a4fe4e1e74beffa979069b353f236ca4c18a51bb
- Cited by
- 137
- References
- 28
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 7 · 2023: 8 · 2022: 4 · 2021: 10 · 2020: 19 · 2019: 7 · 2018: 9 · 2017: 14 · 2016: 11 · 2015: 14 · 2014: 16 · 2013: 7
- FWCI
- 6.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- NIH (AG034253, AG039708, AG026478, P30NS069329)
- M4M Recipient of Young investigator award
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- histone deacetylase inhibitors, Alzheimer's disease, amyloid-beta, gamma-secretase, MMP-2, learning and memory, tau phosphorylation, blood-brain barrier penetration, epigenetic therapy
- MeSH terms
- Acetamides, Alzheimer Disease, Animals, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Humans, Learning, Memory, Mice, Transgenic, Microinjections, Neurons, Phosphorylation, Thioglycolates, Transfection, Blotting, Western, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, tau Proteins, Maze Learning, Mice, Histone Deacetylase 2, Histone Deacetylase Inhibitors, Real-Time Polymerase Chain Reaction
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 2026-10-17, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-17 (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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