# Biological age acceleration associates with Alzheimer's disease plasma biomarker levels

**Authors:** Jaclyn M. Eissman, Yiyi Ma, Min Qiao, Dolly Reyes‐Dumeyer, Angel Piriz, Annie J. Lee, Rafael A. Lantigua, Martin Medrano, Diones Rivera Mejia, Lawrence S. Honig, Francine Grodstein, David A. Bennett, Philip L. De Jager, Clifton L. Dalgard, Richard Mayeux, Badri N. Vardarajan

PMC · DOI: 10.1002/alz.71005 · 2026-01-22

## TL;DR

This study finds that biological age, measured through blood methylation, is linked to Alzheimer's disease biomarkers in a Hispanic population.

## Contribution

The study shows biological age acceleration is associated with plasma AD biomarkers in a non-European cohort.

## Key findings

- Age acceleration was significantly associated with P-tau217 and other plasma biomarkers.
- Biomarker associations were stronger in APOE-ε4 non-carriers.
- CD4 and CD8 T-cell methylation levels correlate with age acceleration.

## Abstract

Epigenetic clocks associate with neuropathology and Alzheimer's disease (AD) clinical risk, but findings are mixed regarding whether clocks associate with blood‐based biomarkers and in non‐European populations.

We calculated biological age and age acceleration from blood methylation data in 704 older Hispanic adults and tested associations with clinical diagnosis and antemortem biomarker levels.

Age acceleration was significantly associated with sex, clinical diagnosis, and levels of eight plasma biomarkers, including P‐tau217 levels. Additionally, biomarker associations trended more significantly among APOE‐ε4 non‐carriers. We also identified that methylation levels in CD4 and CD8 T‐cell types are associated with age acceleration.

We demonstrated that biological age acceleration, measured in blood, in a Hispanic cohort enriched for preclinical individuals, can stratify clinical AD risk and is associated with plasma AD biomarker levels.

Blood‐based aging clocks associate with Alzheimer's disease plasma biomarker levels.Biological aging appears relevant to pathological aging in apolipoprotein E (APOE) ‐ε4 non‐carriers.Immune T‐cell composition relates to biological aging.

Blood‐based aging clocks associate with Alzheimer's disease plasma biomarker levels.

Biological aging appears relevant to pathological aging in apolipoprotein E (APOE) ‐ε4 non‐carriers.

Immune T‐cell composition relates to biological aging.

## Linked entities

- **Proteins:** APOE (apolipoprotein E)
- **Diseases:** Alzheimer's disease (MONDO:0004975)

## Full-text entities

- **Genes:** NEFL (neurofilament light chain) [NCBI Gene 4747] {aka CMT1F, CMT2E, CMTDIG, NF-L, NF68, NFL}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, TET2 (tet methylcytosine dioxygenase 2) [NCBI Gene 54790] {aka IMD75, KIAA1546, MDS}, GFAP (glial fibrillary acidic protein) [NCBI Gene 2670] {aka ALXDRD}
- **Diseases:** MCI (MESH:D060825), neurofibrillary tangle (MESH:D055956), RESEARCH (MESH:D014947), death (MESH:D003643), cognitive decline (MESH:D003072), amyloid (MESH:C000718787), AD (MESH:D000544), Dementia (MESH:D003704), neurodegeneration (MESH:D019636)
- **Chemicals:** bisulfite (MESH:C042345), 5-methylcytosine (MESH:D044503), cystines (MESH:D003553), 5-hydroxymethylcytosine (MESH:C011865), P (MESH:D010758), ROS (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12828061/full.md

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Source: https://tomesphere.com/paper/PMC12828061