ArticlemedRxiv : the preprint server for health sciences2026
Proteomics signatures associated with cognitive trajectories: evidence from the English Longitudinal Study of Ageing.
Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors.
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Abstract
Alzheimer's disease and related dementias (ADRD) pose a growing global health challenge, with early detection critical to slowing cognitive decline and prevent ADRD. We analyzed high-throughput plasma proteomics in 2,460 cognitively healthy adults from the English Longitudinal Study of Ageing (ELSA) to identify proteins linked to 15-year cognitive trajectories, including verbal fluency, episodic memory, and orientation. Mixed-effect linear models revealed 34 proteins associated with faster orientation decline and 18 with accelerated episodic memory decline. Enrichment analyses implicate extracellular matrix remodeling, immune signaling, apoptosis, and lysosomal-autophagic pathways in cognitive deterioration. Subgroup analyses showed sex-specific effects, highlighting heterogeneity in proteomics signatures in cognitive aging. Notably, ten identified proteins are targets of drugs under clinical investigation, suggesting opportunities for therapeutic repurposing. These findings define a plasma proteomic signature associated with decline in domain-specific cognitive functions, offering promising biomarkers and druggable targets to prevent or slow age-related cognitive decline.
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