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49/100

✓ Peer-reviewed alzhub usefulness score 49 out of 100. Genetics

Topic: Amyloid, tau and blood-test diagnosis

We included 1179 CU subjects (n = 474 females (40%), 70.9 ± 4.5 years old) of European descent who had pTau217 and PACC. Mic-ADPRS was associated with a longitudinal increase in pTau217 (beta = 13.9 x, SE = 2.4 x, p = 0.05). Mic-ADPRS was also associated with faster PACC decline (beta= -15.0 x, SE = 1.8 x, p = < 0.001). Mediation analysis suggests 42% of Mic-ADPRS-PACC association is mediated by increased pTau217. Our findings suggest AD heritability localizing to microglial genes and contribute to increased soluble pTau217 release at a given Aβ burden, which in turn mediates the association between microglial AD genetic risk and cognitive decline. Our results are consistent with previous studies implying microglia in Aβ-related tau accumulation and indicate that much of microglial impact on cognitive decline may occur through accelerated tau pathology in CU older adults.

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APA 7th

Mendez, B. J. G., Teng, L., Marshall, G. A., Liu, L., Chhatwal, J. P., Hohman, T. J., et al. (2025). Microglia‐specific Alzheimer's disease polygenic risk score predicts longitudinal increase in plasma tau and faster cognitive decline in cognitively unimpaired older adults. Alzheimer s & Dementia. https://doi.org/10.1002/alz70856_106441

Vancouver

Mendez BJG, Teng L, Marshall GA, Liu L, Chhatwal JP, Hohman TJ, et al. Microglia‐specific Alzheimer's disease polygenic risk score predicts longitudinal increase in plasma tau and faster cognitive decline in cognitively unimpaired older adults. Alzheimer s & Dementia. 2025. doi:10.1002/alz70856_106441. PMID: 41518606.

BibTeX

@article{mendez2025-41518606,
  author  = {Mendez, Brahyan J. Galindo and Teng, Ling and Marshall, Gad A. and Liu, Lei and Chhatwal, Jasmeer P. and Hohman, Timothy J. and Mayeux, Richard P and De Jager, Philip L. and others},
  title   = {{Microglia‐specific Alzheimer's disease polygenic risk score predicts longitudinal increase in plasma tau and faster cognitive decline in cognitively unimpaired older adults}},
  journal = {Alzheimer s \& Dementia},
  year    = {2025},
  doi     = {10.1002/alz70856_106441},
  pmid    = {41518606},
  url     = {https://doi.org/10.1002/alz70856_106441}
}

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Key findings

We included 1179 CU subjects (n = 474 females (40%), 70.9 ± 4.5 years old) of European descent who had pTau217 and PACC.
Mic-ADPRS was associated with a longitudinal increase in pTau217 (beta = 13.9 x, SE = 2.4 x, p = 0.05).
Mic-ADPRS was also associated with faster PACC decline (beta= -15.0 x, SE = 1.8 x, p = < 0.001).
Mediation analysis suggests 42% of Mic-ADPRS-PACC association is mediated by increased pTau217.
Our findings suggest AD heritability localizing to microglial genes and contribute to increased soluble pTau217 release at a given Aβ burden, which in turn mediates the association between microglial AD genetic risk and cognitive decline.

Why it matters

In cognitively unimpaired older adults, a microglia-specific Alzheimer polygenic risk score predicted a longitudinal increase in plasma tau and faster cognitive decline. The findings suggest that much of the microglial effect on cognitive decline may occur through accelerated tau pathology, but no treatment is tested.

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Study details

Study designlongitudinal study
Participants474
Evidence strengthModerate

How this study scored 49/100

Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and randomised / blinded because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Alzheimer s & Dementia)
Journal's citation record	2 / 4	Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29)
Study design	7 / 12	A longitudinal study following the same people over time
Strength of evidence	3 / 5	Rated “moderate” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	4 / 5	2025 — within 3 year(s) of the newest study here
Sample size	2 / 4	474 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 3 year(s) since 2025
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	2 / 4	Last-listed author Hyun‐Sik Yang: h-index 34 (OpenAlex, whole career)
Institution's track record	3 / 3	Harvard University: institution h-index 3,235 (OpenAlex)
Multi-centre collaboration	2 / 3	OpenAlex lists 9 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 41518606)
Free to read	2 / 2	Free to read
Total	49 / 100	—

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

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