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

Shvetcov, Artur; Johnson, Erik C. B.; Winchester, Laura; Walker, Keenan A.; Wilkins, Heather; Thompson, Terri G.; Rothstein, Jeffrey D.; Krish, Varsha; Imam, Farhad; Burns, Jeffrey M.; Swerdlow, Russell H.; Slawson, Chad; Finney, Caitlin A.

doi:10.1038/s41591-025-03835-z

articleNature MedicineJul 15, 2025HYBRID OA

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

ASArtur Shvetcov ECErik C. B. Johnson LWLaura Winchester KAKeenan A. Walker HWHeather Wilkins

The University of Sydney · Westmead Institute for Medical Research · +11 more institutions

PubMed

Indexed incrossrefpubmed

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…

Citation impact

55

total citations

FWCI: 34.69
Percentile: 100%
References: 89

Citations per year

Authors

13

Topics & keywords

Topics

Keywords

Neurodegeneration
Apolipoprotein E
Frontotemporal dementia
Disease
Amyotrophic lateral sclerosis
Immune system
Dementia
Neuroinflammation

No related works found for this paper.