Longitudinal Association of a Polygenic Risk Score for Plasma T-Tau With Incident Alzheimer Dementia and Mild Cognitive Impairment
Niki Mourtzi, Sokratis Charisis, Eva Ntanasi, Alexandros Hatzimanolis, Alfredo Ramı́rez, Stefanos N. Sampatakakis, Mary Yannakoulia, Mary H. Kosmidis et al.. Neurology, 2025-10-03
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
In the HELIAD sample, among 618 cognitively healthy participants (mean age 73.37 years, 58.4% female), followed for 2.92 ± 0.80 years, 73 developed AD/aMCI. A 1 SD increase in PRStau was linked to a 29% higher AD/aMCI risk (hazard ratio [HR] 1.290, 95% CI 1.006-1.654). Stratified analyses revealed greater effect estimates in women (HR 1.451, 95% CI 1.023-2.058) and younger participants (HR 1.866, 95% CI 1.175-2.962), whereas results in men and older participants did not reach statistical significance. In the UKB sample (n = 142,637, mean age 64.2 years, 52% female), 2,737 participants developed AD over 12.9 ± 2.4 years of follow-up. Higher PRStau was also linked to increased AD risk (HR 1.046, 95% CI 1.007-1.086). These results support the potential utility of PRS for plasma t-tau in predicting AD/aMCI incidence. The relationship between genetic predisposition for elevated plasma t-tau levels and AD pathology might be influenced by sex and age, suggesting that these factors should be considered in AD genetic risk modeling. PRS could serve as an early indicator of genetic propensity for tau pathology, enhancing existing AD diagnostic and risk stratification algorithms.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Mourtzi, N., Charisis, S., Ntanasi, E., Hatzimanolis, A., Ramı́rez, A., Sampatakakis, S. N., et al. (2025). Longitudinal Association of a Polygenic Risk Score for Plasma T-Tau With Incident Alzheimer Dementia and Mild Cognitive Impairment. Neurology. https://doi.org/10.1212/wnl.0000000000213904
Vancouver
Mourtzi N, Charisis S, Ntanasi E, Hatzimanolis A, Ramı́rez A, Sampatakakis SN, et al. Longitudinal Association of a Polygenic Risk Score for Plasma T-Tau With Incident Alzheimer Dementia and Mild Cognitive Impairment. Neurology. 2025. doi:10.1212/wnl.0000000000213904. PMID: 41043097.
BibTeX
@article{mourtzi2025-41043097,
author = {Mourtzi, Niki and Charisis, Sokratis and Ntanasi, Eva and Hatzimanolis, Alexandros and Ramı́rez, Alfredo and Sampatakakis, Stefanos N. and Yannakoulia, Mary and Kosmidis, Mary H. and others},
title = {{Longitudinal Association of a Polygenic Risk Score for Plasma T-Tau With Incident Alzheimer Dementia and Mild Cognitive Impairment}},
journal = {Neurology},
year = {2025},
doi = {10.1212/wnl.0000000000213904},
pmid = {41043097},
url = {https://doi.org/10.1212/wnl.0000000000213904}
}
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Key findings
- In the HELIAD sample, among 618 cognitively healthy participants (mean age 73.37 years, 58.4% female), followed for 2.92 ± 0.80 years, 73 developed AD/aMCI.
- A 1 SD increase in PRStau was linked to a 29% higher AD/aMCI risk (hazard ratio [HR] 1.290, 95% CI 1.006-1.654).
- Stratified analyses revealed greater effect estimates in women (HR 1.451, 95% CI 1.023-2.058) and younger participants (HR 1.866, 95% CI 1.175-2.962), whereas results in men and older participants did not reach statistical significance.
- In the UKB sample (n = 142,637, mean age 64.2 years, 52% female), 2,737 participants developed AD over 12.9 ± 2.4 years of follow-up.
- Higher PRStau was also linked to increased AD risk (HR 1.046, 95% CI 1.007-1.086).
Why it matters
A genetic score for plasma tau levels was associated with a higher risk of developing Alzheimer dementia or mild cognitive impairment in two large samples. The effect appeared stronger in women and younger participants, but the study does not show that this score can prevent or treat the disease.
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Study details
- Participants142,637
- Effect size58.4%; or 2.92; HR 1.451
- Evidence strengthLow
How this study scored 49/100
Published in a leading specialty journal. Scored zero for study design and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 4 / 4 | 142,637 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization 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 | 3 / 4 | Last-listed author Nikolaos Scarmeas: h-index 90 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Massachusetts Institute of Technology: institution h-index 2,557 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 21 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41043097) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 100 | — |
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