The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index; none of the 34 sources its claims cite is checked for support yet.
Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease
Open accessAbstract
SUMMARY To elucidate the role of Tau isoforms and post-translational modification (PTM) stoichiometry in Alzheimer’s disease (AD), we generated a high-resolution quantitative proteomics map of 95 PTMs on multiple isoforms of Tau isolated from postmortem human tissue from 49 AD and 42 control subjects. Although Tau PTM maps reveal heterogeneity across subjects, a subset of PTMs display high occupancy and frequency for AD, suggesting importance in disease. Unsupervised analyses indicate that PTMs occur in an ordered manner, leading to Tau aggregation. The processive addition and minimal set of PTMs associated with seeding activity was further defined by analysis of size-fractionated Tau. To summarize, features in the Tau protein critical for disease intervention at different stages of disease are identified, including enrichment of 0N and 4R isoforms, underrepresentation of the C terminus, an increase in negative charge in the proline-rich region (PRR), and a decrease in positive charge in the microtubule binding domain (MBD).
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This study used quantitative mass spectrometry to map tau post-translational modifications in postmortem brain from Alzheimer’s disease and control donors, finding heterogeneous but ordered modification patterns that track disease stage. It identifies isoform shifts and charge-related modifications linked to aggregation and seeding.
Key findings
Across 49 AD and 42 control subjects, 95 PTMs at 88 residues were mapped, including 55 phosphorylation, 17 ubiquitination, 19 acetylation, and 4 methylation sites; insoluble tau was about 100-fold higher in AD (~1,000 vs ~10 fmol/mg), while soluble tau was lower (~3,000 vs ~5,000 fmol/mg). Insoluble AD tau was enriched for 0N and 4R isoforms; N-terminal and C-terminal regions were underrepresented, proline-rich region phosphorylation was high, and microtubule-binding-domain acetylation/ubiquitination increased with aggregate size. Unsupervised clustering separated subjects into groups reflecting Braak stage and PTM burden, and a classifier trained on cohort 1 predicted AD pathology in cohort 2 with >0.92 accuracy. Size-fractionated tau showed seeding-competent high-molecular-weight/insoluble species had microtubule-binding-domain modifications and 20 phosphosites in the high-molecular-weight fraction, while seeding-incompetent low-molecular-weight/soluble species were N-terminally enriched and had fewer proline-rich-region phosphosites.
Methods
Postmortem BA39 angular gyrus from 49 AD and 42 matched controls was analyzed, plus BA46 frontal gyrus in 9 controls and 10 AD subjects; high- and low-molecular-weight tau fractions came from 4 AD and 4 control subjects. FLEXITau targeted mass spectrometry quantified absolute tau and isoform-specific peptides, while data-dependent LC-MS/MS mapped PTMs; sarkosyl solubility and size-exclusion/MC1 fractionation separated tau species. Analyses included PCA, hierarchical clustering, PLS-DA, Spearman correlation, and a stochastic gradient descent classifier; data were deposited in ProteomeXchange.
Limitations
Stated: using top-ranked PTMs as biomarkers requires an adequately powered study with suitable specimens, and high-molecular-weight fraction PTM patterns showed patient-to-patient variability. Stated/evident: the postmortem cross-sectional design cannot directly prove temporal order or causality of PTM progression, and some controls had early AD-like PTMs, complicating group boundaries. Evident: some analyses rely on small subsets (BA46 n=19; high-/low-molecular-weight n=8), and stoichiometry for some microtubule-binding-domain sites was around 50%, so not every tau molecule carries those modifications.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
96 Own result · 35 Own interpretation · 19 Not checked yet · 14 Own method · 2 No basis given
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
“Our analysis extended this to 55 phosphorylation sites on pathological insoluble Tau in BA39 and 43 phosphosites in B46 (Figure S2C).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Qualitative and Quantitative Maps of Tau PTMs and Their Frequency in AD Patient
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A 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 median concentrations of pathological insoluble Tau in BA39 were 100-fold higher in AD (~1,000 fmol/mg fresh weight of tissue) compared with controls (~10 fmol/mg fresh weight of tissue) (Figure 1B).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Tau Concentrations and Isoform Distributions in AD and Control Subjects
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
“Interestingly, in soluble Tau, the most abundant species are the 1N and 4R isoforms”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Tau Concentrations and Isoform Distributions in AD and Control Subjects
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A 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
“underrepresentation of the C terminus”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A 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 data and subsequent analyses showed that that the highest-frequency PTMs, isoform distributions, and quantitative profiles of the BA46 region are shared between the two brain regions”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS
plainn = 10- 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
“subjects in these clusters have a significantly higher Tau and amyloid burden in BA39 than subjects falling into clusters a and d (Figure 2B).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Individual Tau PTM Profiles Show Heterogeneity and Reflect Disease Progression
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
“Increased phosphorylation of the PRR is also observed in symptomatic patients in cluster d as well as in AD clusters b and c”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Individual Tau PTM Profiles Show Heterogeneity and Reflect Disease Progression
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
“Although Tau PTM maps reveal heterogeneity across subjects”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > Abstract
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
“The total amount of soluble Tau is lower in AD patients (~3,000 fmol/mg fresh weight of tissue) compared with control subjects (~5,000 fmol/mg fresh weight of tissue) (Figure 1B).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Tau Concentrations and Isoform Distributions in AD and Control Subjects
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
“In particular, the peptides spanning [195–209] and [212–224] that encompass the sites (S198, S199, S202, T205) and (S212, S214, S217) respectively, are observed to be > 90% modified in AD in the FLEXITau data.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Qualitative and Quantitative Maps of Tau PTMs and Their Frequency in AD Patient
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. 41
- Probably not a substantial claim. 27
- The quote only partly states this claim. 1
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
“Cluster d contains 10 symptomatic patients with late stage AD pathology Braak IV-VI and 16 asymptomatic controls at Braak 0–II.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Individual Tau PTM Profiles Show Heterogeneity and Reflect Disease Progression
plainn = 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
“ANOVA analysis showed higher Tau and Ab levels in clusters with a higher Braak stage and increased level of Tau PTMs (Figure 2B).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Individual Tau PTM Profiles Show Heterogeneity and Reflect Disease Progression
plaincorrelationaln = 27- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We identified 95 distinct PTMs on 88 amino acid residues across all samples and fractions, with a cumulative sequence coverage of 96% from detected modified and unmodified 2N4R Tau peptides (Figure 1E).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Qualitative and Quantitative Maps of Tau PTMs and Their Frequency in AD Patient
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
“Some of the 88 sites of modification mapped are modified by a single type of PTM; however, others can carry multiple types of modifications, such as K311, which can be ubiquitinated or acetylated.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Qualitative and Quantitative Maps of Tau PTMs and Their Frequency in AD Patient
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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 this study, we show that 17 ubiquitin sites are specific to pathological Tau (14 in BA46; Figure S2C).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Qualitative and Quantitative Maps of Tau PTMs and Their Frequency in AD Patient
boostedcorrelational- 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
“A large percentage of AD patients cluster into two major groups (Figure 2A, b and c), whereas the controls fall into two clusters (Figure 2A, a and d).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Individual Tau PTM Profiles Show Heterogeneity and Reflect Disease Progression
plaincorrelationaln = 27- 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
“Instead, the 1N isoform is depleted significantly, and the 0N isoform is enriched in the insoluble fraction.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Tau Concentrations and Isoform Distributions in AD and Control Subjects
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
“FLEXITau quantified a total of 24 Tau peptides; of these, some were isoform specific, achieving a total sequence coverage of 61% for the 2N4R Tau isoform (Figure 1D).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Tau Concentrations and Isoform Distributions in AD and Control Subjects
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“A high frequency of acetylation occurs in the R4 region, including the sites K353, K369, K370, and K375, whereas ubiquitination occurs in R1–R3.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Qualitative and Quantitative Maps of Tau PTMs and Their Frequency in AD Patient
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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 the insoluble fraction containing pathologic Tau, 0N and 1N Tau were enriched significantly compared with the 2N isoform, and the 4R isoform is enriched significantly compared with the 3R isoform.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Tau Concentrations and Isoform Distributions in AD and Control Subjects
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
“The Braak stage of cluster b is V, whereas the Braak stage of cluster c is VI”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Individual Tau PTM Profiles Show Heterogeneity and Reflect Disease Progression
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
“Nineteen distinct acetylation sites were mapped in BA39 and 18 in BA46.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Qualitative and Quantitative Maps of Tau PTMs and Their Frequency in AD Patient
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“Clusters b and c display many of the same PTMs; however, in cluster c, we observe a higher frequency of several PTMs, including T175, S237, and K281 (and S113, S191, and T205, which are difficult to observe at lower stoichiometry, particularly because S113 is a phosphosite found on a 0N Tau peptide).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Individual Tau PTM Profiles Show Heterogeneity and Reflect Disease Progression
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
“These PTMs include phosphorylation occurring at adjacent sites (S262 and S263), acetylation (K311, K353, and K369), and ubiquitination (K259, K267, K311, and K317).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Individual Tau PTM Profiles Show Heterogeneity and Reflect Disease Progression
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
“These data indicate that there is an increase in the number of PTMs and the occupancy of these PTM sites observed at different stages of disease”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Stoichiometric PTM Maps of Human Pathologic Tau Identify Critical Steps in Disease Progression
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 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
“Our analysis of pathological Tau from 91 subjects (49 AD and 42 control subjects) cumulatively identifies 95 PTMs at 88 aa residues. We mapped 55 phosphosites, 17 ubiquitination sites, 19 acetylation sites, and four methylation sites along the length of the Tau protein.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > DISCUSSION
plainn = 91- 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
“The seeding-incompetent AD and control Tau sarkosyl-soluble fractions show no differences; both are enriched in the N-terminal regions (Figure 4C).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Identifying PTMs Associated with Seeding Activity in Size-Fractionated Tau
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
“Although the unmodified C-terminal peptide is found with low abundance in AD compared to all controls, there is a control cluster where the C terminus is completely unmodified (Figure 3A) and the other control cluster shows some processing.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Tau Peptide Stoichiometry Data Identify Key Pathological Features in Disease
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
“Unsupervised analyses based on the presence or absence of PTMs clustered the subjects into 4 major groups and revealed that there were specific combinations of PTMs in each of these groups.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > 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
“the PRR appears to accumulate phosphosites and the MBD appears to accumulate acetylation and ubiquitination with increasing size of Tau aggregates.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Identifying PTMs Associated with Seeding Activity in Size-Fractionated Tau
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“HMW Tau, which is thought to be oligomeric Tau, displays 20 phosphosites (6 in the N terminus, 10 in the PRR, and 4 in the C-terminal region) as well as 3 acetylation and 4 ubiquitin sites in the MBD.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Identifying PTMs Associated with Seeding Activity in Size-Fractionated Tau
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
“LMW Tau shows a similar modification pattern to Tau as the sarkosyl-soluble fraction, with 6 phosphorylations (T181, S199, S202, and T231) in the PRR being consistently observed sites in LMW and sarkosyl-soluble fractions.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Identifying PTMs Associated with Seeding Activity in Size-Fractionated Tau
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The N-specific region is largely underrepresented (45–67, 68–87, and 88–126), as is the C terminus in AD.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Tau Peptide Stoichiometry Data Identify Key Pathological Features in Disease
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
“Comparative analysis of the two seeding-competent fractions, HMW Tau and the larger, fibrillized, insoluble Tau, shows a similar pattern; however, the MBD is even more enriched in the insoluble Tau fraction, and the peptide 260–267 is underrepresented, indicating a higher phosphorylation stoichiometry of this peptide (S262 and T263).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Identifying PTMs Associated with Seeding Activity in Size-Fractionated Tau
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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 sites include three KXGS motifs”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > DISCUSSION
plainn = 91- 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
“Although acetylation and ubiquitination are observed in the MBD of HMW Tau”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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 patient frequency of these PTMs is high; however, the stoichiometry of these sites is ~50%; thus, every second Tau molecule in a fibril is modified.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > DISCUSSION
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
“Moreover, the increase in these modifications correlates positively with increasing polymer length and increased abundance of pathological Tau associated with disease progression.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > 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.
In the paper
“we previously developed a targeted, high-throughput quantitative mass spectrometry (MS) method called FLEXITau (full-length expressed stable isotope-labeled Tau) (Mair et al., 2016), which provides absolute quantification and unbiased stoichiometric information of Tau PTMs from the N to the C terminus.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > INTRODUCTION
What the sources say
- Not checked yetcites Mair et al., 2016
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Tau forms intracellular neurofibrillary tangles (NFTs) (Grundke-Iqbal et al., 1986; Kosik et al., 1986; Wood et al., 1986)”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > INTRODUCTION
What the sources say
- Not checked yetcites Grundke-Iqbal et al., 1986
- Not checked yetcites Kosik et al., 1986
- Not checked yetcites Wood et al., 1986
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Tens of possible PTM sites have been described for Tau in studies involving in vitro (Hanger et al., 2007; Martin et al., 2013a, 2013b) and in vivo AD mouse models (Morris et al., 2015; Tramutola et al., 2018) and in postmortem human studies (Hanger et al., 2007; Min et al., 2015).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > INTRODUCTION
What the sources say
- Not checked yetcites Hanger et al., 2007
- Not checked yetcites Martin et al., 2013a
- Not checked yetcites Morris et al., 2015 source
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.
In the paper
“Besides phosphorylation, the neurofibrillary aggregates are also subject to a wide range of other PTMs (Hanger et al., 2007)”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > INTRODUCTION
What the sources say
- Not checked yetcites Hanger et al., 2007
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Aβ forms extracellular plaques (Glenner and Wong, 1984; Masters et al., 1985)”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > INTRODUCTION
What the sources say
- Not checked yetcites Glenner and Wong, 1984
- Not checked yetcites Masters et al., 1985
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“pathological neurofibrillary Tau aggregates show a pattern of accumulation that starts in the entorhinal cortex and spreads through connected pathways to cortical areas (Jucker and Walker, 2013)”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > INTRODUCTION
What the sources say
- Not checked yetcites Jucker and Walker, 2013 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
“The majority of subjects in d are listed as control subjects, and these PTMs are likely to be the earliest signs of pathology.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Individual Tau PTM Profiles Show Heterogeneity and Reflect Disease Progression
hedgedconditionaln = 16- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“they cannot accurately measure quantitative changes or determine PTM stoichiometry.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > INTRODUCTION
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.
None of the sources cited for this claim have been checked yet.
In the paper
“The discovery of dominantly inherited Tau mutations leading to frontotemporal dementia (FTD) (Poorkaj et al., 1998; Spillantini et al., 1998)”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > INTRODUCTION
What the sources say
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
“suggesting that early disease is observed in a few controls.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Qualitative and Quantitative Maps of Tau PTMs and Their Frequency in AD Patient
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
None of the sources cited for this claim have been checked yet.
In the paper
“brain lysates seed Tau aggregation when high-molecular-weight oligomeric hyperphosphorylated (AT8 and AT100) Tau species are present (Takeda et al., 2015; Jackson et al., 2016)”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > INTRODUCTION
What the sources say
- Not checked yetcites Takeda et al., 2015 source
- Not checked yetcites Jackson et al., 2016
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Combinations of such PTMs are responsible for regulating and fine-tuning protein conformation and activity (Aebersold et al., 2018; Soria et al., 2014)”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > INTRODUCTION
What the sources say
- Not checked yetcites Aebersold et al., 2018 source
- Not checked yetcites Soria et al., 2014
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“This encompasses a cycle that involves production of a Tau seed followed by uptake of seed-competent Tau into connected cells (Clavaguera et al., 2013)”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > INTRODUCTION
What the sources say
- Not checked yetcites Clavaguera et al., 2013
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggests that the modification at the C terminus is an early event during aging and AD pathology and can most likely be attributed to caspase-3 and −6 cleavage at D418 and D421.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Tau Peptide Stoichiometry Data Identify Key Pathological Features in Disease
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“which has been shown to form the core region of the Tau filaments (Fitzpatrick et al., 2017).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > DISCUSSION
What the sources say
- Not checked yetcites Fitzpatrick et al., 2017
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“which are known to regulate neurite extension and binding of Tau to microtubules (Biernat et al., 1993; Biernat and Mandelkow, 1999).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > DISCUSSION
What the sources say
- Not checked yetcites Biernat et al., 1993
- Not checked yetcites Biernat and Mandelkow, 1999
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. 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
“Importantly, these data suggest that early intervention may need different therapeutic agents than late-stage AD because there are distinct differences in PTM profiles associated with each stage of disease.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: unclear — It is unclear whether it could 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
“This increase in phosphorylation of Tau may be involved in neutralizing the charge in the MBD domain to promote aggregation”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Tau Peptide Stoichiometry Data Identify Key Pathological Features in Disease
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The sets of PTMs were largely reflective of disease progression and therefore could be associated with disease stages.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > DISCUSSION
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The above results from sarkosyl-insoluble (fibrillized) Tau from AD and control subjects indicate that there is processivity and an order in which PTMs occur in the fibrillization process.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Identifying PTMs Associated with Seeding Activity in Size-Fractionated Tau
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.
In the paper
“an observation partially consistent with recent Tau PTM mapping results in mice (Morris et al., 2015; Table S5).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > DISCUSSION
What the sources say
- Not checked yetcites Morris et al., 2015 source
hedgedcorrelationaln = 91- 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
“To ensure no bias in acquisition, samples were run in randomized order (three technical replicates per sample).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > METHOD DETAILS > Preparation of brain tissue samples and mass spectrometry analysis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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
“In addition, all MS/MS spectra of identified post-translationally modified peptides were subjected to manual verification.”
- Also stated in: § Preparation and MS analysis of MC1-isolated Tau · plain
“Spectra for identified modified peptides were manually validated.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > METHOD DETAILS > Preparation of high and low molecular weight Tau and mass spectrometric 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.
- Also stated in: § Preparation and MS analysis of MC1-isolated Tau · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that the 0N and 4R version, when phosphorylated, is no longer disordered and can adopt a structure capable of fibril formation.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > 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
“In addition, all MS/MS spectra of identified post-translationally modified peptides were subjected to manual verification.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > METHOD DETAILS > Preparation of brain tissue samples and mass spectrometry analysis
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
“All peptide transitions were evaluated for variability, similarity between y-ion ratios, elution times, and interfering signals by manual analysis.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > METHOD DETAILS > Preparation of brain tissue samples and mass spectrometry analysis
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
“Peptides were considered ‘quantifiable’ if the peptide transitions had a signal-to-noise of > 3 and at least three light and three heavy high-quality SRM transitions were observed.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > METHOD DETAILS > Preparation of brain tissue samples and mass spectrometry analysis
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.
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
“which would be charged positively at physiological pH and experience repulsive electrostatic forces, preventing formation of a b sheet fibril structure.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > 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.
- Rests on an assumption: Tau contains 19 lysine residues in its microtubule-binding domain.
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
“Increased phosphorylation in the PRR results in accumulation of negative charges, which, we postulate, could neutralize the positive charge in the MBD”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
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
“False discovery rate (FDR) was set to 1% on peptide and protein levels with a minimum length of seven amino acids and was determined by searching a reverse database.”
- Also stated in: § Preparation and MS analysis of MC1-isolated Tau · plain
“False discovery rate (FDR) was set to 1% on peptide and protein level and was determined by searching a reverse database.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > METHOD DETAILS > Preparation of brain tissue samples and mass spectrometry analysis
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.
- Also stated in: § Preparation and MS analysis of MC1-isolated Tau · plain
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
“Randomized samples (SEC fractions 2,3,4 and 14,16,18 for 4 AD and 4 control human brain samples) were analyzed in duplicates using a Q Exactive mass spectrometer”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > METHOD DETAILS > Preparation of high and low molecular weight Tau and mass spectrometric analysis
plainn = 4- 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
“Randomized samples (SEC fractions 2,3,4 and 14,16,18 for 4 AD and 4 control human brain samples) were analyzed in duplicates using a Q Exactive mass spectrometer”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > METHOD DETAILS > Preparation of high and low molecular weight Tau and mass spectrometric analysis
plainn = 4- 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
“A cutoff of 85% confidence was employed for all modified peptides.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > METHOD DETAILS > Preparation of high and low molecular weight Tau and mass spectrometric analysis
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
“Peak boundaries were manually inspected and reassigned as needed to ensure correct peak detection and accurate integration.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > METHOD DETAILS > Preparation of brain tissue samples and mass spectrometry analysis
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
“A cutoff of 85% confidence was employed for all modified peptides.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > METHOD DETAILS > Preparation of brain tissue samples and mass spectrometry 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 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 support a processive model (Figure 5C) where 0N and 4R are predisposed to aggregation, cleavage of the C terminus enables fibrillization, followed by phosphorylation in the PRR domain and acetylation and ubiquitination in the MBD, which remove electrostatic repulsion of positively charged lysine residues in this region, promoting Tau fibrilization.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > 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.
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
“Western Blot analysis using Tau13, Tau46, HT7 and DAKO antibodies confirmed that the fraction 3 and 4 are enriched for Tau (data not shown).”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > METHOD DETAILS > Preparation of high and low molecular weight Tau and mass spectrometric analysis
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The authors state this as an assumption.
A qualitative and quantitative approach using a large cohort of human AD subjects had not been performed before this study.
“To our knowledge, a qualitative and quantitative approach using a large cohort of human AD subjects has not been performed.”
The authors state this as an assumption.
The minimum set of PTMs important for oligomer formation and Tau aggregation is not known.
“Furthermore, the minimum set of PTMs important for oligomer formation and Tau aggregation is not known.”
The authors state this as an assumption.
Which PTMs occur on Tau seeds that can potentiate further aggregation is not known.
“Finally, it is not known which PTMs occur on Tau seeds that can potentiate further aggregation.”
The paper relies on this without support.
Tau contains 19 lysine residues in its microtubule-binding domain.
“Tau has 19 lysine residues in the MBD”
The paper relies on this without support.
The disordered regions of Tau include the N terminus and the proline-rich region.
“The disordered regions of Tau span the N terminus and PRR.”
The paper relies on this without support.
HMW Tau is oligomeric Tau.
“HMW Tau, which is thought to be oligomeric Tau”
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?
In the citing paper
“In examining the clinical records, we found that those cases with the most marked propagation potential also had the fastest clinical course and had characteristic patterns of post-translational modifications (10, 11).”
From All the Tau We Cannot See (2023) · cites this paper as [11]
In the citing paper
“For example, the microtubule-associated protein tau is often measured using antibodies that represent phosphorylation at threonine 181 and one that measures so called “total-tau”. However, at least 95 post-translational modifications have been discovered on tau with potentially many 100s of possible proteoforms resulting from the combinations.(16)”
From Putting humpty dumpty back together again: what does protein quantification mean in bottom-up proteomics? (2022) · cites this paper as [16]
In the citing paper
“Additional studies indicate that specific tau phosphosites may be better indicators of disease progression, emphasizing the importance of distinguishing between different pTau isoforms and proteoforms.(15,16)”
From Putting humpty dumpty back together again: what does protein quantification mean in bottom-up proteomics? (2022) · cites this paper as [16]
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 major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Identifying PTMs Associated with Seeding Activity in Size-Fractionated Tau
“we observe acetylation and ubiquitination as being unique to seeding-positive Tau compared with LMW and sarkosyl-soluble seeding-negative fractions.”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > DISCUSSION
“Ubiquitination is unique to seeding-competent Tau, whereas acetylation is also observed in seeding-incompetent Tau.”
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
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Individual Tau PTM Profiles Show Heterogeneity and Reflect Disease Progression
“These PTMs include phosphorylation occurring at adjacent sites (S262 and S263)”
§ Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease > RESULTS > Identifying PTMs Associated with Seeding Activity in Size-Fractionated Tau
“indicating a higher phosphorylation stoichiometry of this peptide (S262 and T263).”
Citations
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 2×
“Selected subjects had the least possible concurrent pathologies and were assessed for Braak NFT stages (Braak and Braak, 1991), as determined by the location of NFTs with total Tau immunostaining and Bielschowsky’s silver stain.”
BackgroundMethodCox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855 · cited 1×
“10 (Cox and Mann, 2008) and peptide list searched against the Homo sapiens Uniprot protein sequence database (December 2017, only reviewed entries appended with common laboratory contaminants [cRAP database, 247 entries]) using the Andromeda search engine (Cox et al.”
MethodAmyloid 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
Universal sample preparation method for proteome analysis
Wiśniewski, J. R., Zougman, A., Nagaraj, N., & Mann, M. (2009) · Nature Methods · doi:10.1038/nmeth.1322 · Cited by 8,352
Andromeda: A Peptide Search Engine Integrated into the MaxQuant Environment
Cox, J., Neuhauser, N., Michalski, A., Scheltema, R. A., Olsen, J. V., & Mann, M. (2011) · Journal of Proteome Research · doi:10.1021/pr101065j · Cited by 5,520 · cited 1×
“10 (Cox and Mann, 2008) and peptide list searched against the Homo sapiens Uniprot protein sequence database (December 2017, only reviewed entries appended with common laboratory contaminants [cRAP database, 247 entries]) using the Andromeda search engine (Cox et al., 2011).”
MethodGlenner, G. G., & Wong, C. W. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(84)80190-4 · Cited by 5,404 · cited 1×
“Aβ forms extracellular plaques (Glenner and Wong, 1984; Masters et al., 1985), whereas Tau forms intracellular neurofibrillary tangles (NFTs) (Grundke-Iqbal et al.”
BackgroundCox, J., Hein, M. Y., Luber, C. A., Paron, I., Nagaraj, N., & Mann, M. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.031591 · Cited by 5,180 · cited 1×
“Label-free quantification was done using the XIC-based in-built label-free quantification (LFQ) algorithm (Cox et al., 2014) integrated into MaxQuant.”
MethodMirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961 · cited 1×
“Inclusion in the study required a highconfidence postmortem neuropathological diagnosis of AD, based on relevant criteria (Montine et al., 2016; Mirra et al., 1991), for the clinical AD group or no more than low AD neuropathological change (Montine et al.”
MethodSkyline: an open source document editor for creating and analyzing targeted proteomics experiments
MacLean, B., Tomazela, D. M., Shulman, N., Chambers, M., Finney, G. L., Frewen, B., Kern, R., Tabb, D. L., Liebler, D. C., & MacCoss, M. J. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq054 · Cited by 4,697
Amyloid plaque core protein in Alzheimer disease and Down syndrome.
Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.4245 · Cited by 4,431 · cited 1×
“Aβ forms extracellular plaques (Glenner and Wong, 1984; Masters et al., 1985), whereas Tau forms intracellular neurofibrillary tangles (NFTs) (Grundke-Iqbal et al.”
Background
Research works printed but not linked: 2
- Lê, 2008, FactoMineR: A Package for Multivariate Analysis, J. Stat. Softw., 25
- Lovestone, 1997, The phosphorylation of tau: a critical stage in neurodevelopment and neurodegenerative processes, Neuroscience, 78, 309
Cited by
Sorted by citations
Items 501–600 of 723
nP-collabs: Investigating counterion mediated bridges in the multiply phosphorylated tau-R2 repeatPreprint
Marien, J., Prévost, C., & Sacquin‐Mora, S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.18.590060 · Cited by 3
Tau phosphorylation suppresses oxidative stress-induced mitophagy via FKBP8 receptor modulationPreprint
Isei, M. O., Crockett, M., Chen, E., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.05.602170 · Cited by 3
Structural Insights into the Role of the Proline Rich Region in Tau FunctionPreprint
Acosta, K., Brue, C. R., Kim, H. J., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.20.614010 · Cited by 3
Seed structure and phosphorylation in the fuzzy coat impact tau seeding competencyPreprint
Kasen, A., Lövestam, S., Breton, E., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.07.642026 · Cited by 3
Ayasse, N. D., Stewart, W. F., Lipton, R. B., Gómez‐Ulloa, D., & Runken, M. C. (2024) · Current Alzheimer Research · doi:10.2174/0115672050316936240905064215 · Cited by 2
Reid, M. J., Leija‐Salazar, M., Troakes, C., Lynham, S., Srivastava, D. P., Perez‐Nievas, B. G., & Noble, W. J. (2025) · iScience · doi:10.1016/j.isci.2025.112793 · Cited by 2
Bone-Derived Factors: Regulating Brain and Treating Alzheimer’s Disease
Guan, Q., Cao, Y., Zou, J., & Zhang, L. (2025) · Biology · doi:10.3390/biology14091112 · Cited by 3
Jaramillo, C. J., Nedderman, D. M., Ahat, E., McElwee, J. L., Soper, M. D., Ballard, D. W., Zhang, L., Credille, K. M., Heady, G., Hsi, E. D., et al. (2025) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlaf108 · Cited by 2
Fang, K., Jiao, B., Shen, L., & Luo, S. (2025) · Brain Informatics · doi:10.1186/s40708-025-00277-8 · Cited by 2
Top‐Down Proteomics Study of Aging and Sexual Dimorphism of Zebrafish Brains
Askarani, M. F., Poulos, W., Dashtaki, M. R., Sadeghi, S. A., Cibelli, J. B., Fang, F., & Sun, L. (2025) · Journal of Mass Spectrometry · doi:10.1002/jms.70009 · Cited by 2
Sex-specific effects of acetylation on tauopathy in aging htau mice
Sabir, U., Csubak, B. A., Ilchenko, S., ANSARI, M. Y. K., Kanaan, N. M., Tsai, T., Srinivasan, D., Dengler-Crish, C. M., & Kasumov, T. (2026) · Scientific Reports · doi:10.1038/s41598-026-41691-0 · Cited by 2
Tau pathology in epilepsy: emerging mechanisms and translational opportunities
Sen, A., Tai, X. Y., Galanopoulou, A. S., Thom, M., Aronica, E., Vivash, L. E., Hardmeier, M., Amos, A., Rüegg, S. J., Koepp, M. J., et al. (2026) · Brain · doi:10.1093/brain/awag108 · Cited by 2
Kanoria, S., Veitch, D. P., Miller, M. J., Aisen, P. S. S., Beckett, L. A., Green, R. C., Harvey, D. J., Jack, C. R., Jagust, W. J., Lee, E. B., et al. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71353 · Cited by 2
Post-translational modifications as a regulatory code for tau function in health and disease
Nordbeck, A. J., Sharma, B., Garcia, C. A., & Tseng, J. (2026) · Frontiers in Dementia · doi:10.3389/frdem.2026.1834737 · Cited by 3
The emerging nontraditional roles for tau in the brain
Tseng, J., & Cohen, T. J. (2023) · Cytoskeleton · doi:10.1002/cm.21811 · Cited by 2
In situ seeding assay: A novel technique for direct tissue localization of bioactive tau
Perbet, R., de Gérando, A. M., Glynn, C. A., Donahue, C., Gaona, A., Taddei, R. N., Gómez‐Isla, T., Lathuilière, A., & Hyman, B. T. (2024) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlae059 · Cited by 2
Self-citationmicroRNAs Mediate Signaling Pathways in Alzheimer’s Disease: Biomarkers and Therapeutic Targets
Rezayof, A., Ghasemzadeh, Z., & Kouhkan, F. (2024) · Springer eBooks · doi:10.1007/978-3-030-80662-0_39 · Cited by 2
Biomarkers for Neurodegenerative Diseases
Abdelmoaty, M. M., Lu, E., & Foster, E. G. (2024) · Springer eBooks · doi:10.1007/978-3-031-68237-7_44 · Cited by 2
Deciphering the role of TYK2 in tau phosphorylation and pathology
Fröhlich, A., & Bowles, K. R. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2025.01.004 · Cited by 2
Higashi, Y., Ikuno, K., Saito, T., Saido, T. C., Miyasaka, T., Kakuda, N., & Funamoto, S. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152025 · Cited by 2
Roy, E. R., Wang, Q., Huang, K., Li, S., Fan, Y., Escobar, E., Atkins, C. L., Huang, S., Herrera, J. J., Li, W., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-12869-9 · Cited by 5
Hiort, P., Schlaffner, C. N., Steen, J. A. J., Renard, B. Y., & Steen, H. (2022) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00669 · Cited by 2
Self-citationTau in Health and Neurodegenerative Diseases
Chu, D., & Liu, F. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.101299 · Cited by 2
Frontotemporal lobar degeneration
Kim, B., Viera-Ortiz, A., Phan, J. M., Irwin, D. J., & Lee, E. B. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-85654-6.00041-1 · Cited by 3
Novel Conformation-Dependent Tau Antibodies Are Modulated by Adjacent Phosphorylation Sites
Paterno, G., Torrellas, J., Bell, B. M., Gorion, K.-M. M., Quintin, S. S., Hery, G. P., Prokop, S., & Giasson, B. I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813676 · Cited by 2
Genome-wide association study and functional validation implicates JADE1 in tauopathyPreprint
Farrell, K. W., Kim, S., Han, N., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.06.30.450599 · Cited by 2
Self-citationTaylor, L. W., Simzer, E. M., Pimblett, C., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.28.553851 · Cited by 2
Mammeri, N. E., Dregni, A. J., Duan, P., & Hong, M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.04.556256 · Cited by 2
Lee, J., Lee, K., Kim, M. S., Kim, M. W., Lim, M., Yoo, J., & Lee, S. H. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.19.563032 · Cited by 2
Martín‐Ávila, A., Modak, S. R., Rajamohamedsait, H. B., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.21.595198 · Cited by 2
Mohl, G. A., Dixon, G., Marzette, E., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.04.597496 · Cited by 2
Huang, M., & McEwan, W. A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.18.604077 · Cited by 2
Mattioni, A., Carsetti, C., Bruqi, K., Caputo, V., Cianfanelli, V., Bacalini, M. G., Casa, M., Gabelli, C., Giardina, E., Cestra, G., et al. (2024) · medRxiv · doi:10.1101/2024.08.13.24311780 · Cited by 2
Impact of multiple phosphorylations on the tau-R2/tubulin interfacePreprint
Marien, J., Prévost, C., & Sacquin‐Mora, S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.19.638976 · Cited by 2
Shultz, A., Vincze, A., Yau, T. T., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.23.661190 · Cited by 2
Distribution of big tau isoforms in the human central and peripheral nervous systemPreprint
Koppitsetti, R. K., Barthélemy, N. R., Horie, K., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.15.676127 · Cited by 2
Application of a Novel Endpoint Staging Framework: Proof of Concept in the AMBAR Study
Podger, L., Stewart, W. F., Serrano, D., Lipton, R. B., Gómez‐Ulloa, D., Ayasse, N. D., Barnes, F. B., Davis, E. A., & Runken, M. C. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-231197 · Cited by 1
Quantification of Methylation and Phosphorylation Stoichiometry
Ayoub, C. A., Moore, K. I., & Kuret, J. (2024) · Methods in molecular biology · doi:10.1007/978-1-0716-3629-9_13 · Cited by 1
SIRT3 differentially regulates lysine benzoylation from SIRT2 in mammalian cells
Peng, P., Lu, Y., Ren, X., et al. (2024) · iScience · doi:10.1016/j.isci.2024.111176 · Cited by 1
Chen, X., Wei, S., & Yang, F. (2024) · Methods in molecular biology · doi:10.1007/978-1-0716-4298-6_17 · Cited by 1
Phospho-Tau Signature During Mitosis: AT8, p-T217 and p-S422 as Key Phospho-Epitopes
Goussard, M., Zarka, K., Denus, M., Curel, T., Claeysen, S., Lefebvre, B., Hamdane, M., Marin, P., Villeneuve, J., & Parmentier, M. (2025) · Cells · doi:10.3390/cells14201638 · Cited by 1
Wu, Q., van den Wildenberg, S. A. H., Brzoskowski, J. C. R., van den Oetelaar, M. C. M., Verhoef, C. J. A., Genet, S. A. A. M., Ottmann, C., Markvoort, A. J., Brunsveld, L., & Cossar, P. J. (2025) · Chemical Science · doi:10.1039/d4sc07419j · Cited by 1
Deciphering Proteoform Landscape of Mammary Carcinoma by Top-Down Proteomics
Knott, S. J., Tucholski, T., Josyer, H., Inman, D. R., Friedl, A., Zhu, Y., Ge, Y., & Ponik, S. M. (2025) · Journal of Proteome Research · doi:10.1021/acs.jproteome.4c01044 · Cited by 1
Urschbach, M., Huhmann, S., Appel, D., Ferrari, L., Vogl, D. P., Martens, S., & Becker, C. F. W. (2025) · Angewandte Chemie · doi:10.1002/ange.202502638 · Cited by 1
Detecting Alzheimer's Disease (Gender-Based) Using Different Machine Learning Approaches
Negi, H. S., Indu, R., Dimri, S. C., Kumar, B., Bisht, N., & Gupta, A. (2025) · International Computer Science Conference · doi:10.1109/icsc64553.2025.10968947 · Cited by 1
A novel pThr217 tau monoclonal antibody reveals neuropathological heterogeneity in tauopathies
Paterno, G., Bell, B. M., Gorion, K.-M. M., Quintin, S. S., Prokop, S., & Giasson, B. I. (2025) · Scientific Reports · doi:10.1038/s41598-025-04291-y · Cited by 2
Hromádková, L., Kim, C., Haldiman, T., Siddiqi, M. K., Surewicz, K. A., Urquhart, K., Sadruddin, D.-E.-N., Peng, L., Zhu, X., Surewicz, W. K., et al. (2025) · PLoS Pathogens · doi:10.1371/journal.ppat.1012926 · Cited by 2
Vegas‐Gomez, L., Pizarro, M., Garcia-Martin, J., Arredondo-Alcala, M. A., Bustamante, B., Gonzalez‐Silva, C., Matus, S., Díaz‐Espinoza, R., Gutiérrez, A., Morales, R., et al. (2025) · PLoS ONE · doi:10.1371/journal.pone.0328470 · Cited by 2
Neuropathology and Biomarker Correlates of Late Onset Alzheimer’s Disease in Aged Old World Monkeys
Zeiss, C. J., Duque, A., & Huttner, A. J. (2025) · Toxicologic Pathology · doi:10.1177/01926233251388069 · Cited by 2
Tau proteoforms as plasma biomarkers in Alzheimer’s disease: mechanisms, measurement, and medicine
Kim, E., Lee, J. H., & Han, D. (2025) · Expert Review of Proteomics · doi:10.1080/14789450.2025.2611853 · Cited by 1
Park, C., Jung, J., Hong, Y., Yoo, H., Yang, K., Shin, J., Kim, M., Lim, C. S., Jeong, A., Hong, S., et al. (2026) · Nature Communications · doi:10.1038/s41467-025-67888-x · Cited by 2
Silva-Martínez, G. A., Cervantes‐Montelongo, J. A., Tristán-Flores, F. E., & de la Rocha, C. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1716675 · Cited by 2
Xiang, Y., Du, X., Yang, H., Wang, P., Yin, B., Wang, Z., Wang, H., Liu, L., Zhang, H., Ren, Y., et al. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03443-4 · Cited by 1
Tsaka, G., Pagès, A. M., Sousa, C. B. D., Lammertyn, J., Walkiewicz, G., Gomes, L. A., Imbrechts, M., Tops, S., Rajasekhar, K., Muwonge, K., et al. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.111221 · Cited by 1
Full-length tau seeded by C-shaped tau fibrils is conformationally variable
Zhang, J. Y., Mammeri, N. E., & Hong, M. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.111315 · Cited by 1
Vesely, C. H., Stanisheuski, S., Lien, E., Reardon, P. N., Chung, P. J., Mehl, R. A., & Cooley, R. B. (2026) · Protein Science · doi:10.1002/pro.70520 · Cited by 1
Predifferentiation Neurotoxicity of GenX Exposure on hiPSC-Derived Cortical Neurons
Wu, S., Xie, J., Zhao, X., Zhao, H., Sánchez, O. F., Yu, S., Rochet, J.-C., Freeman, J. L., & Yuan, C. (2026) · Environmental Science & Technology · doi:10.1021/acs.est.5c13193 · Cited by 2
Zhou, J., Liu, J., Liu, X., Ren, L., Yu, Z., Zheng, Z., & Li, G. (2026) · Science Advances · doi:10.1126/sciadv.aeb2729 · Cited by 1
Monoclonal antibodies and small molecules: on the cutting edge of Alzheimer’s disease therapy
Ouro, A., Ben-Dor, G. A., Debasa‐Mouce, M., Gulkarov, S., Leon, J. D., Castro‐Mosquera, M., Sobrino, T., Bougea, A. M., & Reiss, A. B. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1766762 · Cited by 1
Dao, S., Cui, C., He, W., Liu, E., Zhang, L., & Tang, H. (2026) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2026.118874 · Cited by 1
Lashuel, H. A. (2026) · Nature Structural & Molecular Biology · doi:10.1038/s41594-026-01792-w · Cited by 1
Polyamine and tau: a chemical framework for understanding the hyperphosphorylated tau condensation
Lee, J., Lee, K. ‐., Kim, M., Kim, M. K., Lim, M., Yoo, J., & Lee, S. H. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.152366 · Cited by 1
Lövestam, S., Wagstaff, J. L., Katsinelos, T., Shi, J., Freund, S. M. V., Goedert, M., & Scheres, S. H. W. (2026) · eLife · doi:10.7554/elife.104778.4 · Cited by 3
Water‐Mediated Phosphoryl Wires Stabilize Pathological Tau Fibrils
Potnuru, L. R., DuBose, A., Mon, F., Nowotarski, M. S., Vigers, M. P., Zhang, B., Han, C.-T., Straub, J. E., & Han, S. (2026) · Angewandte Chemie · doi:10.1002/ange.202521499 · Cited by 1
Skrehot, J. T., & Kurouski, D. (2026) · Protein Science · doi:10.1002/pro.70635 · Cited by 2
Zhang, L., Yang, C., Yao, Q., Du, X., Ding, S., Shi, Y., Sheng, C., Wang, M., Han, Y., & Luo, H. (2026) · Advanced Science · doi:10.1002/advs.75983 · Cited by 2
Oosterlynck, M., Fichter, L., Leroux, É., Eddarkaoui, S., Bouillet, T., Lefebvre, C., Nguyen, M., Maurage, C., Accart, B., Dupré, E., et al. (2026) · Journal of Biomedical Science · doi:10.1186/s12929-026-01250-1 · Cited by 1
Spatial transcriptomics in Alzheimer's disease: technologies, challenges and discoveries
Shi, C. H., Piña-Crespo, J., Yip, K. Y., & Huang, T. Y. (2026) · Molecular Neurodegeneration Advances · doi:10.1186/s44477-026-00036-x · Cited by 3
Molecular and environmental drivers of tau post-translational modifications and tau pathology
Price, T. M., Tucker, A. E., & Funk, K. E. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103223 · Cited by 2
CSF and plasma tau biomarkers in the Down syndrome–Alzheimer’s disease continuum
Arranz, J., Lantero‐Rodriguez, J., Braun-Wohlfahrt, L. S., Vaqué‐Alcázar, L., Rodríguez‐Baz, Í., Kac, P. R., Arslan, B., Maure‐Blesa, L., Pertierra, L., Videla, L., et al. (2026) · EBioMedicine · doi:10.1016/j.ebiom.2026.106370 · Cited by 2
Zaman, W., Ayaz, A., & Ullah, A. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118275 · Cited by 2
Bellver‐Sanchís, A., Ralchev, N., Romanska, P. R., Dyakova, N. K., Ivanova, K. I., Griñán‐Ferré, C., & Marchev, A. S. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27177833 · Cited by 1
Large-scale single-molecule analysis of tau proteoforms
Joly, J. H., Budamagunta, V., Zhang, Z., Nortman, B., Jouzi, M., Bhatnagar, R., Egertson, J. D., Flaster, M. E., Grothe, R., Guha, S. K., et al. (2026) · Nature Methods · doi:10.1038/s41592-026-03188-6 · Cited by 10
Targeting tau degradation: a viable therapeutic approach?
Mason, M., Bacioglu, M., Vivacqua, G., Spillantini, M. G., & Tolkovsky, A. M. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(23)00108-4 · Cited by 1
Schneeweis, A. K., & Pak, D. T. S. (2023) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2023.106475 · Cited by 1
Site‐Specific Ubiquitination of Tau Amyloids Promoted by the E3 Ligase CHIP
Parolini, F., Kachoie, E. A., Leo, G., Civiero, L., Bubacco, L., Arrigoni, G., Munari, F., Assfalg, M., D’Onofrio, M., & Capaldi, S. (2023) · Angewandte Chemie · doi:10.1002/ange.202310230 · Cited by 1
Five biomarkers from one cerebrospinal fluid sample to stage Alzheimer’s disease
Salvadó, G., & Hansson, O. (2024) · Nature Aging · doi:10.1038/s43587-024-00618-y · Cited by 1
Insights from a proteomic atlas of human Alzheimer’s disease brain tissue
Kavanagh, T., & Drummond, E. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00215 · Cited by 2
dGAE(297–391) Tau Fragment Promotes Formation of Chronic Traumatic Encephalopathy‐Like Tau Filaments
Kitoka, K., Lends, A., Kučinskas, G., Bula, A. L., Krasauskas, L., Smirnovas, V., Žilková, M., Kováčech, B., Škrabana, R., Hritz, J., et al. (2024) · Angewandte Chemie · doi:10.1002/ange.202407821 · Cited by 1
NEXT-GEN Medicine: Designing Drugs to Fit Patient Profiles
Kamal, R., Diksha, D., Paul, P., Awasthi, A., & Singh, A. (2024) · Current Bioinformatics · doi:10.2174/0115748936316656240830080555 · Cited by 1
Biomarkers used in Alzheimer's disease diagnosis
Mishra, S. K., Singh, R., Chang, H., Obaid, A. A., & Singh, S. K. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15540-6.00013-6 · Cited by 1
Mätlik, K., Pressl, C., & Heintz, N. (2025) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-112723-025516 · Cited by 1
Neurodegeneration: 2021 update
Crary, J. F. (2021) · Free Neuropathology · doi:10.17879/freeneuropathology-2021-3317 · Cited by 1
In situ neuroregeneration: frontiers and therapeutic prospects
Wang, Q., Li, W., Lei, W., Chen, W., Zheng, J., Xiang, Z., MinHui, L. I. U., He, Q., Xu, L., Li, Z., et al. (2021) · Scientia Sinica Vitae · doi:10.1360/ssv-2021-0024 · Cited by 1
Theofilas, P., Piergies, A. M. H., Li, S. H., et al. (2021) · medRxiv · doi:10.1101/2021.01.28.21250322 · Cited by 1
Self-citationAguilar-Pineda, J. A., Vera-López, K. J., Shrivastava, P., Nieto-Montesinos, R., Chávez‐Fumagalli, M. Á., Dávila-Del-Carpio, G., Valdez, B. G., Miller, C. L., Malhotra, R. K., Lindsay, M. E., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.13.439741 · Cited by 1
Tracy, T. E., Madero-Pérez, J., Swaney, D., Chang, T. S., Moritz, M., Konrad, C., Ward, M., Stevenson, E., Hüttenhain, R., Kauwe, G., et al. (2021) · bioRxiv · doi:10.1101/2021.06.17.448349 · Cited by 1
Phosphorylation of Truncated Tau Promotes Abnormal Native Tau Pathology and NeurodegenerationPreprint
Li, L., Jiang, Y., Wu, G., et al. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3903546 · Cited by 1
Hsp multichaperone complex buffers pathologically modified TauPreprint
Moll, A., Ramirez, L. M., Ninov, M., Schwarz, J., Urlaub, H., & Zweckstetter, M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.03.18.484853 · Cited by 1
Huang, Z., Merrihew, G. E., Larson, E. B., Park, J., Plubell, D. L., Fox, E. J., Montine, K. S., Keene, C. D., Zou, J., MacCoss, M. J., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.09.511430 · Cited by 1
Murray, M. E., Moloney, C. M., Kouri, N., et al. (2022) · medRxiv · doi:10.1101/2022.10.12.22280971 · Cited by 1
Tau amyloid polymorphism is shaped by local structural propensities of its protein sequencePreprint
Louros, N. N., Wilkinson, M., Tsaka, G., Ramakers, M., Morelli, C., Garcia, T., Gallardo, R. U., D’Haeyer, S., Goossens, V., Audenaert, D., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.24.512987 · Cited by 1
Yang, H., Yuan, P., Wu, Y., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.01.526692 · Cited by 1
Romero‐Fernandez, W., Carvajal‐Tapia, C., Prusky, A., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-2570335/v1 · Cited by 1
Site-specific phosphorylation of tau impacts mitochondrial biology and response to stressorsPreprint
Isei, M. O., Girardi, P., Rodwell‐Bullock, J., Nehrke, K. W., & Johnson, G. V. W. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.19.529131 · Cited by 1
García-Cruz, V. M., & Arias, C. (2023) · Research Square · doi:10.21203/rs.3.rs-2909341/v1 · Cited by 1
Characterization and super-resolution imaging of small tau aggregates in human samplesPreprint
Böken, D., Cox, D., Burke, M., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.12.544575 · Cited by 1
Chemical Synthesis of Microtubule-Associated Protein Tau 2N4RPreprint
Powell, W. C., Jing, R., & Walczak, M. A. A. (2023) · ChemRxiv · doi:10.26434/chemrxiv-2023-js9bp
Metadata
- Authors
- Wesseling, H., Mair, W., Kumar, M., Schlaffner, C. N., Tang, S., Beerepoot, P., Fatou, B., Guise, A. J., Cheng, L., Takeda, S., Muntel, J., Rotunno, M. S., Dujardin, S., Davies, P., Kosik, K. S., Miller, B. L., Berretta, S., Hedreen, J. C., Grinberg, L. T., Seeley, W. W., Hyman, B. T., Steen, H., & Steen, J. A.
- Affiliations
- Boston Children's Hospital (US)
- Harvard University (US)
- Feinstein Institute for Medical Research (US)
- University of California, Santa Barbara (US)
- University of California, San Francisco (US)
- Corresponding author
- Steen, Judith A.
- ORCID
- Kumar, Mukesh
- Schlaffner, Christoph N.
- Tang, Shaojun
- Beerepoot, Pieter
- Fatou, Benoit
- Guise, Amanda J.
- Cheng, Long
- Takeda, Shuko
- Muntel, Jan
- Dujardin, Simon
- Davies, Peter
- Kosik, Kenneth S.
- Miller, Bruce L.
- Berretta, Sabina
- Hedreen, John C.
- Grinberg, Lea T.
- Seeley, William W.
- Hyman, Bradley T.
- Steen, Hanno
- Steen, Judith A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 183
- Issue
- 6
- Pages
- 1699-1713.e13
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC8168922
- OpenAlex
- W3102160053
- Semantic Scholar
- eb7657dfe7b98f7376299bf9d45805d3dc70eb6d
- Cited by
- 688
- References
- 78
- Citations by year
- 2026: 104 · 2025: 132 · 2024: 140 · 2023: 112 · 2022: 109 · 2021: 88 · 2020: 2
- FWCI
- 47.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- Tau Consortium
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- Alzheimer's disease, tau protein, post-translational modification, tau isoforms, tau aggregation, seeding activity, patient heterogeneity, disease staging, proline-rich region, microtubule-binding domain, postmortem brain, quantitative proteomics
- MeSH terms
- Alzheimer Disease, Humans, Protein Processing, Post-Translational, Cohort Studies, Case-Control Studies, tau Proteins, Disease Progression, Protein Isoforms, Principal Component Analysis
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 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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
