APOE ε4 carriers share immune-related proteomic changes across neurodegenerative diseases.

ABSTRACT: The APOE ε4 genetic variant is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) and is increasingly being implicated in other neurodegenerative diseases. Using the Global Neurodegeneration Proteomics Consortium SomaScan dataset covering 1,346 cerebrospinal fluid (CSF) and 9,924 plasma samples, we used machine learning-based proteome profiling to identify an APOE ε4 proteomic signature shared across individuals with AD, frontotemporal dementia (FTD), Parkinson's disease dementia (PDD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and nonimpaired controls. This signature was enriched in pro-inflammatory immune and infection pathways as well as immune cells, including monocytes, T cells and natural killer cells. Analysis of the dorsolateral prefrontal

SUBMITTER: Shvetcov A 

PROVIDER: S-EPMC12353839 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature