Plasma extracellular vesicles from APOE3 Christchurch carriers display a protective phenotype in early stages of autosomal dominant Alzheimer's disease.

ABSTRACT:

Introduction

The PSEN1^E280A mutation causes autosomal dominant Alzheimer's disease (ADAD) with predictable onset, enabling presymptomatic studies. Extracellular vesicles (EVs) are emerging biomarkers of cognitive decline, but their role in early ADAD is unclear. The rare apolipoprotein E (APOE3) Christchurch (APOE3^Ch) variant delays disease onset, yet its effect on EVs is unknown.

Methods

We analyzed plasma EVs from mild cognitive impairment (MCI) and non-MCI PSEN1^E280A-APOE3 carriers and non-MCI PSEN1^E280A-APOE3^Ch carriers using flow cytometry, proteomics, and co-culture assays.

Results

APOE3^Ch-EVs showed reduced vascular activation and inflammatory cargo linked to β-catenin signaling, higher apoE leve

SUBMITTER: Pineda-Lopez L 

PROVIDER: S-EPMC12823782 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature