DNA damage-associated oligodendrocyte degeneration precedes amyloid pathology and contributes to Alzheimer's disease and dementia.

ABSTRACT:

Introduction

In looking for novel non-amyloid-based etiologies for Alzheimer's disease, we explore the hypothesis that age-related myelin loss is an attractive explanation for age-associated cognitive decline and dementia.

Methods

We performed a meta-analysis of data in the National Alzheimer's Coordinating Center database accompanied by quantitative histopathology of myelin and oligodendrocytes (OLs) in frontal cortices of 24 clinically characterized individuals. Pathological findings were further validated in an Alzheimer's disease mouse model and in culture.

Results

Myelin lesions increased with cognitive impairment in an amyloid-independent fashion with signs of degeneration appearing before neuronal loss. Myelinating OLs in the gray matter showed greater vulnerab

SUBMITTER: Tse KH 

PROVIDER: S-EPMC5938117 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature