Glucocorticoids Increase Amyloid-beta and Tau Pathology in a Mouse Model of Alzheimer's Disease

Overview

Journal J Neurosci

Specialty Neurology

Date 2006 Sep 1

PMID 16943563

Citations 293

Authors

Kim N Green

Lauren M Billings

Benno Roozendaal

James L McGaugh

Frank M LaFerla

Affiliations

Soon will be listed here.

Abstract

Various environmental and genetic factors influence the onset and progression of Alzheimer's disease (AD). Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which controls circulating levels of glucocorticoid hormones, occurs early in AD, resulting in increased cortisol levels. Disturbances of the HPA axis have been associated with memory impairments and may contribute to the cognitive decline that occurs in AD, although it is unknown whether such effects involve modulation of the amyloid beta-peptide (Abeta) and tau. Using in vitro and in vivo experiments, we report that stress-level glucocorticoid administration increases Abeta formation by increasing steady-state levels of amyloid precursor protein (APP) and beta-APP cleaving enzyme. Additionally, glucocorticoids augment tau accumulation, indicating that this hormone also accelerates the development of neurofibrillary tangles. These findings suggest that high levels of glucocorticoids, found in AD, are not merely a consequence of the disease process but rather play a central role in the development and progression of AD.

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