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Association of epigenetic aging with plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation in Hispanic/Latino adults
Myriam Fornage, Wassim Tarraf, Martha L. Daviglus, Charles S DeCarli, Kevin A. González, Carmen R. Isasi, Sayaka Kuwayama, Melissa Lamar et al.. Clinical Epigenetics, 2025-08-01
Topic: Brain proteins, microglia and lab models
Blood-based biomarkers hold significant promise for the early detection and diagnosis of Alzheimer’s disease (AD) and other dementias. Age-related changes in blood levels of AD biomarkers are well-documented but poorly understood. Epigenetic clocks are mathematical models based on DNA methylation patterns that reflect various aspects of the multidimensional aging process. We investigated the associations of epigenetic aging with five blood-based AD biomarkers in 2656 Hispanic/Latino adults (mean age 62.5 years; 65% females) from the Hispanic Community Health Study/Study of Latinos. We used multivariable linear regression models to estimate the associations of acceleration in each of five epigenetic clocks with each biomarker in the total sample and in sex-specific strata, controlling for chronological age, sex (except in sex-stratified analyses), Hispanic/Latino background, recruitment site, risk factors, and comorbid medical conditions. There were varying strengths of association between acceleration of the clocks and the plasma biomarkers. There were significant associations of acceleration in all epigenetic clocks with higher plasma levels of neurofilament light chain (NfL) (Beta = 0.0045 to 0.0193; P = 0.022 to 4.9 × 10 –15 ). There were significant associations of acceleration in all epigenetic clocks except DunedinPACE with higher plasma levels of amyloid beta (Aβ)40 (Beta = 0.0033 to 0.0049; P = 0.024 to 1.7 × 10 –5 ). PC-PhenoAge acceleration was associated with all circulating biomarkers but its associations with Aβ42, Aβ42/40 ratio, and phosphorylated Tau 181 (p-Tau181) showed heterogeneity by sex. Specifically, PC-PhenoAge acceleration was associated with higher Aβ42 and p-Tau181 levels in males (Beta = 0.0066, P = 0.002 and Beta = 0.0158, P = 2 × 10 –4 , respectively) but not females, while it was associated with lower Aβ42/40 ratio in females (Beta = − 0.0032, P = 0.012) but not males. Epigenetic age acceleration is associated with circulating biomarkers of AD in Hispanic/Latino adults. The second‐generation clock PC-PhenoAge showed strong and consistent associations across all biomarkers, and thus may reflect biological processes most relevant to age-related changes in AD biomarkers. Considering sex differences in the relationship between biological aging and circulating AD biomarkers is paramount.
Key findings
- Blood-based biomarkers hold significant promise for the early detection and diagnosis of Alzheimer’s disease (AD) and other dementias.
- There were significant associations of acceleration in all epigenetic clocks with higher plasma levels of neurofilament light chain (NfL) (Beta = 0.0045 to 0.0193; P = 0.022 to 4.9 × 10 –15 ).
- There were significant associations of acceleration in all epigenetic clocks except DunedinPACE with higher plasma levels of amyloid beta (Aβ)40 (Beta = 0.0033 to 0.0049; P = 0.024 to 1.7 × 10 –5 ).
- PC-PhenoAge acceleration was associated with all circulating biomarkers but its associations with Aβ42, Aβ42/40 ratio, and phosphorylated Tau 181 (p-Tau181) showed heterogeneity by sex.
- Specifically, PC-PhenoAge acceleration was associated with higher Aβ42 and p-Tau181 levels in males (Beta = 0.0066, P = 0.002 and Beta = 0.0158, P = 2 × 10 –4 , respectively) but not females, while it was associated with lower Aβ42/40 ratio in females (Beta = − 0.0032, P = 0.012) but not males.
Why it matters
This study of 2,656 Hispanic/Latino adults found significant associations between acceleration in epigenetic clocks and higher plasma levels of neurofilament light chain and amyloid beta 40. It examines relationships between aging measures and blood biomarkers, which may aid early detection, but no treatment, cure, or prevention was tested.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Clinical Epigenetics) |
| Journal's citation record | 1 / 4 | Clinical Epigenetics: journal h-index 114 (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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 3.2× 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 | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Hector M. González: h-index 39 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Minnesota: institution h-index 1,568 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40750903) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
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Read the original
- DOI: 10.1186/s13148-025-01941-w
- PubMed: 40750903
- Original source →
- Free full text: Clinical Epigenetics →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Fornage, M., Tarraf, W., Daviglus, M. L., DeCarli, C. S., González, K. A., Isasi, C. R., et al. (2025). Association of epigenetic aging with plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation in Hispanic/Latino adults. Clinical Epigenetics. https://doi.org/10.1186/s13148-025-01941-w
Vancouver
Fornage M, Tarraf W, Daviglus ML, DeCarli CS, González KA, Isasi CR, et al. Association of epigenetic aging with plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation in Hispanic/Latino adults. Clinical Epigenetics. 2025. doi:10.1186/s13148-025-01941-w. PMID: 40750903.
BibTeX
@article{fornage2025-40750903,
author = {Fornage, Myriam and Tarraf, Wassim and Daviglus, Martha L. and DeCarli, Charles S and González, Kevin A. and Isasi, Carmen R. and Kuwayama, Sayaka and Lamar, Melissa and others},
title = {{Association of epigenetic aging with plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation in Hispanic/Latino adults}},
journal = {Clinical Epigenetics},
year = {2025},
doi = {10.1186/s13148-025-01941-w},
pmid = {40750903},
url = {https://doi.org/10.1186/s13148-025-01941-w}
}
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