Mifepristone alters amyloid precursor protein processing to preclude amyloid beta and also reduces tau pathology.

ABSTRACT:

Background

Increased circulating glucocorticoids are features of both aging and Alzheimer's disease (AD), and increased glucocorticoids accelerate the accumulation of AD pathologies. Here, we analyzed the effects of the glucocorticoid receptor antagonist mifepristone (RU486) in the 3xTg-AD mouse model at an age where hippocampal damage leads to high circulating corticosterone levels.

Methods

The effects of mifepristone were investigated in 3xTg-AD mice using a combination of biochemical, histological, and behavior analyses.

Results

Mifepristone treatment rescues the pathologically induced cognitive impairments and markedly reduces amyloid beta (Aβ)-load and levels, as well as tau pathologies. Analysis of amyloid precursor protein (APP) processing revealed concomitant

SUBMITTER: Baglietto-Vargas D 

PROVIDER: S-EPMC3633722 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature