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48/100

✓ Peer-reviewed alzhub usefulness score 48 out of 100. Down syndrome and Alzheimer's

Topic: Brain proteins, microglia and lab models

Individuals with Down syndrome (DS) have an increased risk of developing Alzheimer disease (AD), with nearly all individuals exhibiting AD neuropathology, including amyloid beta (Aβ) plaques and neurofibrillary tangles (NFT), by age 40 years. Fluid AD biomarker studies highlight an increase in several phosphorylated tau (p-tau) epitopes in DS. However, neuropathological measures of p-tau epitopes in DS have not been examined. Therefore, our main objective was to characterize p-tau epitope burdens across the DS lifespan at autopsy. We analyzed postmortem brain samples of 98 individuals with late-onset AD (LOAD), DS with AD neuropathology (DSAD), young DS (below 40 years of age), and age-matched neurotypical controls, ranging from 1 to 96 years of age. Immunohistochemical and digital pathology measures of p-tau epitopes at threonine 181 (pThr181), threonine 217 (pThr217), and threonine 231 (pThr231) burdens in the frontal cortex were compared across groups. We observed similar pThr181, pThr217, and pThr231 burdens between DSAD and LOAD, despite DSAD cases being younger on average. Observed pThr181, pThr217, and pThr231 burdens were higher in DSAD compared to young DS and neurotypical controls. Generalized additive models (GAMs) were used to model the cross-sectional trajectory of p-tau epitope burdens across the DS lifespan. Estimated age breakpoints revealed a significant rise in frontal cortex pThr231 at age 40, followed by pThr181 and pThr217 at age 42. In summary, our findings revealed an age-associated increase in p-tau epitopes across the DS lifespan. Our results have the potential to inform future associations between neuropathological and biofluid and neuroimaging biomarker measures of p-tau epitopes.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Pascual, JR., Rivera, I., Nguyen, H., Ngo, P. T., Hoang, A., Andrews, E. J., et al. (2026). Neuropathological measures of increased tau phosphorylation across the Down syndrome lifespan. Acta neuropathologica. https://doi.org/10.1007/s00401-026-02994-8

Vancouver

Pascual JR, Rivera I, Nguyen H, Ngo PT, Hoang A, Andrews EJ, et al. Neuropathological measures of increased tau phosphorylation across the Down syndrome lifespan. Acta neuropathologica. 2026. doi:10.1007/s00401-026-02994-8. PMID: 41865347.

BibTeX

@article{pascual2026-41865347,
  author  = {Pascual, JR. and Rivera, I. and Nguyen, H. and Ngo, P. T. and Hoang, A. and Andrews, E. J. and Rouanet, J. and Wright, S. T. and others},
  title   = {{Neuropathological measures of increased tau phosphorylation across the Down syndrome lifespan}},
  journal = {Acta neuropathologica},
  year    = {2026},
  doi     = {10.1007/s00401-026-02994-8},
  pmid    = {41865347},
  url     = {https://doi.org/10.1007/s00401-026-02994-8}
}

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Key findings

Individuals with Down syndrome (DS) have an increased risk of developing Alzheimer disease (AD), with nearly all individuals exhibiting AD neuropathology, including amyloid beta (Aβ) plaques and neurofibrillary tangles (NFT), by age 40 years.
We observed similar pThr181, pThr217, and pThr231 burdens between DSAD and LOAD, despite DSAD cases being younger on average.
Observed pThr181, pThr217, and pThr231 burdens were higher in DSAD compared to young DS and neurotypical controls.
Estimated age breakpoints revealed a significant rise in frontal cortex pThr231 at age 40, followed by pThr181 and pThr217 at age 42.
In summary, our findings revealed an age-associated increase in p-tau epitopes across the DS lifespan.

Why it matters

In postmortem brain samples, burdens of three phosphorylated tau epitopes were similar between Down syndrome with Alzheimer's disease and late-onset Alzheimer's disease, and higher than in young Down syndrome and neurotypical controls. This is a cross-sectional autopsy study and reports no treatment or prevention.

Study details

Study designcross-sectional
Participants98
Evidence strengthLow

How this study scored 48/100

Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 46 of the 96 points we could judge it on, which is 48 out of 100.

Component	Points	Why
Journal tier	9 / 10	Tier 2 — leading specialty journal (Acta neuropathologica)
Journal's citation record	3 / 4	Acta Neuropathologica: journal h-index 287 (OpenAlex, 2026-10-29)
Study design	4 / 12	A snapshot of people at one point in time
Strength of evidence	1 / 5	Rated “low” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	5 / 5	2026 — within 1 year(s) of the newest study here
Sample size	1 / 4	98 participants
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	3 / 3	Studied in people (participant count stated)
Randomised / blinded	0 / 2	No randomisation or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	0 / 7	Cited 0 times (OpenAlex, 2026-10-10)
Citations per year	0 / 5	0.0 citations a year over 2 year(s) since 2026
Impact for its field and year	0 / 6	Cited 0.0× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	0 / 6	No other study in this library cites it
Still being cited	0 / 4	Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	— / 4	OpenAlex's profile for last-listed author Fan Zhang holds only 1 work(s), too few to judge a track record — left out of this score
Institution's track record	3 / 3	Harvard University: institution h-index 3,235 (OpenAlex)
Multi-centre collaboration	3 / 3	OpenAlex lists 10 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 41865347)
Free to read	2 / 2	Free to read
Points	46 / 96	Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 46 of the 96 points we could judge it on is 48 out of 100.
Total	48 / 100	—

What each of these 20 components measures, and what this score is not →

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