ArticleMolecular neurodegeneration2024
Proteomic analysis of APOEε4 carriers implicates lipid metabolism, complement and lymphocyte signaling in cognitive resilience.
Article in Molecular neurodegeneration, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Early axonal degeneration linked to clinical decline in Alzheimer's disease progression revealed with diffusion MRI.The Journal of clinical investigation · 2026Trial
- Alzheimer's Disease and MERC Dysfunction: Integrating Mechanisms, Biomarkers, and Therapeutic Strategies.Molecular neurobiology · 2026Review
- Plasma inflammatory biomarker profiles across the Alzheimer's disease spectrum in the Bio-Hermes cohort.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Plasma Proteomic Analysis ofmedRxiv : the preprint server for health sciences · 2026Article
- OMG! A proteomic determinant of neurodegenerative resiliency.Molecular neurodegeneration · 2026Article
- Effect sizes of APOE e4 on the same general cognitive ability test taken by the same people from age 11 to age 90: The Lothian Birth Cohorts 1921 and 1936.Molecular psychiatry · 2026Article
- DNA Methylation Signatures of Systemic Inflammation Are Associated With Brain Volume, Cognitive Trajectories, and Long-Term Dementia Risk.Aging cell · 2025Article
- Axonal Degeneration Across the Alzheimer's Disease Spectrum: A Longitudinal MRI and Fluid Biomarker Study.medRxiv : the preprint server for health sciences · 2025Article
- Molecular pathogenesis of Alzheimer's disease onset in a mouse model: effects of cannabidiol treatment.Frontiers in neuroscience · 2025Article
- The proteomic and metabolomic signature of inherited chromosomally integrated HHV-6 and its role in all-cause dementia and mortality risk: The UK Biobank study.Alzheimer's & dementia (New York, N. Y.)Article
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19 authors.
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Abstract
backgroundApolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late onset Alzheimer's disease (AD). This case-cohort study used targeted plasma biomarkers and large-scale proteomics to examine the biological mechanisms that allow some APOEε4 carriers to maintain normal cognitive functioning in older adulthood.
methodsAPOEε4 carriers and APOEε3 homozygotes enrolled in the Women's Health Initiative Memory Study (WHIMS) from 1996 to 1999 were classified as resilient if they remained cognitively unimpaired beyond age 80, and as non-resilient if they developed cognitive impairment before or at age 80. AD pathology (Aß
resultsA total of 1610 participants were included (baseline age: 71.3 [3.8 SD] years; all White; 42% APOEε4 carriers). Compared to resilient APOEε4 carriers, non-resilient APOEε4 carriers had lower Aß
conclusionsWe identified and replicated a plasma proteomic signature associated with cognitive resilience among APOEε4 carriers. These proteins implicate specific immune processes in the preservation of cognitive status despite elevated genetic risk for AD. Future studies in diverse cohorts will be needed to assess the generalizability of these results.
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