DNA Damage Increases Secreted Aβ40 and Aβ42 in Neuronal Progenitor Cells: Relevance to Alzheimer's Disease.

ABSTRACT:

Background

Recent studies suggest a strong association between neuronal DNA damage, elevated levels of amyloid-β (Aβ), and regions of the brain that degenerate in Alzheimer's disease (AD).

Objective

To investigate the nature of this association, we tested the hypothesis that extensive DNA damage leads to an increase in Aβ40 and Aβ42 generation.

Methods

We utilized an immortalized human neuronal progenitor cell line (NPCs), ReN VM GA2. NPCs or 20 day differentiated neurons were treated with hydrogen peroxide or etoposide and allowed to recover for designated times. Sandwich ELISA was used to assess secreted Aβ40 and Aβ42. Western blotting, immunostaining, and neutral comet assay were used to evaluate the DNA damage response and processes indicative of AD pathology.

SUBMITTER: Welty S 

PROVIDER: S-EPMC9277680 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature