Protective mechanisms against Alzheimer's disease in APOE3-Christchurch homozygous astrocytes.

ABSTRACT:

Introduction

Alzheimer's disease (AD) is characterized by tau pathology, leading to neurodegeneration. Astrocytes regulate central nervous system homeostasis and influence AD progression. The APOE3-Christchurch (APOE3-Ch) variant is linked to AD resilience, but its protective mechanisms remain unclear.

Methods

Human induced pluripotent stem cell-derived astrocytes (APOE3-Ch and wild type) were used to assess tau uptake, clearance, lipid metabolism, and transcriptomic adaptations. Fluorescently labeled 2N4R-P301L tau oligomers were tracked, and pathway-specific inhibitors dissected tau clearance mechanisms. Lipidomic and transcriptomic analyses were performed to identify genotype-specific adaptations.

Results

APOE3-Ch astrocytes exhibited enhanced tau uptake via hepara

SUBMITTER: Tian X 

PROVIDER: S-EPMC12444642 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature