Journal article
2-aminobutyrate mediates the impact of air pollution on blood biomarkers of Alzheimer's disease
Alzheimer's & dementia, v 22(5), e71388
May 2026
PMID: 42165338
Abstract
We examined the impact of mid-life metabolites on late-life Alzheimer's disease (AD) plasma biomarkers and whether these metabolites mediate air pollution effects.
In the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) cohort, we applied high-dimensional regression and meditation models, adjusting for observed and latent confounders, with replication in the Atherosclerosis Risk in Communities (ARIC) study. Exposures included mid-life fine particulate matter (PM
), black carbon, metals, and metabolites. Outcomes were: late-life plasma p-tau(181, 217, and 231) and amyloid beta 42/40 (Simoa assays).
In the Heart SCORE study, seven lipid- and amnio acid-pathway metabolites measured in mid-life were significantly inversely associated with late-life p-tau181 levels (false discovery rate ≤ 15%) and showed a nominal inverse association with p-tau217 and 231 (P < 0.05). 2-aminobutyrate was associated with mid-life PM
concentration (µg/m
; β = -0.047; P = 4.0 × 10-4) and mediated the effect of PM
on p-tau181 (P = 0.0057). Independent replication in the ARIC study confirmed the inverse association.
Mid-life metabolite profiles, particularly 2-aminobutyrate, may predict and mediate air pollution-related AD risk.
Seven mid-life metabolites were inversely linked to late-life plasma phosphorylated tau (p-tau)181. 2-aminobutyrate was tied to fine particulate matter (PM
), black carbon, and heavy metal exposure in two independent cohorts. 2-aminobutyrate may link pollution to Alzheimer's disease (AD) via oxidative stress pathways. This effect is specific to p-tau181, a marker of early AD changes. This is the evidence of a metabolic mediator between air pollution and AD risk.
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Details
- Title
- 2-aminobutyrate mediates the impact of air pollution on blood biomarkers of Alzheimer's disease
- Creators
- Anum Saeed (Corresponding Author) - University of PittsburghChris Mckennan - University of PittsburghJane E Clougherty - Drexel UniversityPeidi Zhou - The University of Texas Health Science Center at HoustonSheila Tripathy - Drexel UniversityEllen J Kinnee - University of PittsburghJiaxuan Duan - University of PittsburghKevin Kip - UPMC Health SystemXuemei Zeng - University of PittsburghVictor Villemagne - University of PittsburghTharick Pascoal - University of PittsburghMark Mapstone - University of California, IrvineEric A Whitsel - University of North Carolina at Chapel HillOscar I Lopez - University of PittsburghChristie Ballantyne - Baylor College of MedicineThomas K Karikari - University of PittsburghBing Yu - The University of Texas Health Science Center at HoustonSteven Reis - University of PittsburghAnnie Cohen - University of Pittsburgh
- Publication Details
- Alzheimer's & dementia, v 22(5), e71388
- Publisher
- Wiley; HOBOKEN
- Number of pages
- 11
- Grant note
- HT94252320064 / DoD the Department of Psychiatry, University of Pittsburgh the Anbridge Charitable Fund U01 NS131740 U01 NS141777 / NIH/NINDS 23CDA1055489 / by American Heart Association and National Institutes of Health ME-02-384 / the Pennsylvania Department of Health R01 AG083874 U24AG082930 P30 AG066468 RF1 AG077474 R01 AG083156 R37 AG023651 R01 AG025516 R01 AG073267 R01 AG075336 R01 AG072641 P01 AG025204 / NIH/NIA R01 MH108509 / NIMH NIH HHS DAF2255207 / Aging Mind Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Urban Health Collaborative; Environmental and Occupational Health
- Web of Science ID
- WOS:001771580000001
- Other Identifier
- 991022180728204721