Age-Related Oxidative Redox and Metabolic Changes Precede Intraneuronal Amyloid-β Accumulation and Plaque Deposition in a Transgenic Alzheimer's Disease Mouse Model.

ABSTRACT:

Background

Many identified mechanisms could be upstream of the prominent amyloid-β (Aβ) plaques in Alzheimer's disease (AD).

Objective

To profile the progression of pathology in AD.

Methods

We monitored metabolic signaling, redox stress, intraneuronal amyloid-β (iAβ) accumulation, and extracellular plaque deposition in the brains of 3xTg-AD mice across the lifespan.

Results

Intracellular accumulation of aggregated Aβ in the CA1 pyramidal cells at 9 months preceded extracellular plaques that first presented in the CA1 at 16 months of age. In biochemical assays, brain glutathione (GSH) declined with age in both 3xTg-AD and non-transgenic controls, but the decline was accelerated in 3xTg-AD brains from 2 to 4 months. The decline in GSH correlated exponentially wit

SUBMITTER: Pontrello CG 

PROVIDER: S-EPMC9789488 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature