Apolipoprotein ε4 exacerbates white matter impairment in a mouse model of Aβ amyloidosis by decreasing actively myelinating oligodendrocytes.

ABSTRACT:

Introduction

The ε4 allele of the apolipoprotein E (APOE) gene is a risk factor for the development of Alzheimer's disease (AD). APOE4 isoform is associated with increased white matter lesions in humans. To identify the underlying mechanisms of white matter impairment associated with APOE4, we investigated the effects of APOE4 and APOE3 on multiple readouts of the white matter microstructural integrity.

Methods

Using magnetic resonance imaging and immunohistochemistry approaches, we analyzed white matter tracts in 5xFAD mice expressing APOE3 (5xFAD;APOE3) or APOE4 (5xFAD;APOE4).

Results

APOE4 significantly decreased fractional anisotropy, axial diffusivity, and neurite density index, while increasing radial diffusivity and isotropic volume fraction within major white

SUBMITTER: Al-Amin MM 

PROVIDER: S-EPMC12514940 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature