ArticleAnnals of clinical and translational neurology2025
APOE genotype and brain amyloid are associated with changes in the plasma proteome in elderly subjects without dementia.
Article in Annals of clinical and translational neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Youth-associated protein TIMP2 regulates microglial state and function in healthy and aged mice.Nature communications · 2026Article
- Proteomics signatures associated with cognitive trajectories: evidence from the English Longitudinal Study of Ageing.medRxiv : the preprint server for health sciences · 2026Article
- Plasma Proteomic Analysis ofmedRxiv : the preprint server for health sciences · 2026Article
- Proteomic signatures and mitochondrial dysfunctions in peripheral T cells reveal novel ınsights into Alzheimer's disease.Scientific reports · 2025Article
- APOE4 promotes nigral tau hyperphosphorylation through cholesterol in atherosclerosis.Cell death discovery · 2025Article
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Authors and funding
4 authors.
Funding
Abstract
objectiveRecent work has bolstered the possibility that peripheral changes may be relevant to Alzheimer's disease pathogenesis in the brain. While age-associated blood-borne proteins have been targeted to restore function to the aged brain, it remains unclear whether other dysfunctional systemic states can be exploited for similar benefits. Here, we investigate whether APOE allelic variation or presence of brain amyloid are associated with plasma proteomic changes and the molecular processes associated with these changes.
methodsUsing the SOMAscan assay, we measured 1305 plasma proteins from 53 homozygous, APOE3 and APOE4 subjects without dementia. We investigated the relationship of either the APOE-ε4 allele or amyloid positivity with plasma proteome changes by linear mixed effects modeling and ontology-based pathway and module-trait correlation analyses.
resultsAPOE4 is associated with plasma protein differences linked to atherosclerosis, tyrosine kinase activity, cholesterol transport, extracellular matrix, and synaptogenesis pathways. Independent of APOE4, we found that subjects likely harboring brain amyloid exhibit plasma proteome signatures associated with AD-linked pathways, including neurovascular dysfunction.
interpretationOur results indicate that APOE4 status or presence of brain amyloid are associated with plasma proteomic shifts prior to the onset of symptoms, suggesting that systemic pathways in certain risk contexts may be plausible targets for disease modification.
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