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The Journal of Neuroscience, August 30, 2006, 26(35):9047-9056; doi:10.1523/JNEUROSCI.2797-06.2006

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Neurobiology of Disease
Glucocorticoids Increase Amyloid- and Tau Pathology in a Mouse Model of Alzheimer’s Disease

Kim N. Green, Lauren M. Billings, Benno Roozendaal, James L. McGaugh, and Frank M. LaFerla

Department of Neurobiology and Behavior, and Center for the Neurobiology of Learning and Memory, University of California, Irvine, Irvine, California 92697-4545

Correspondence should be addressed to Frank M. LaFerla, Department of Neurobiology and Behavior, University of California, Irvine, 1109 Gillespie Neuroscience Building, Irvine, CA 92697-4545. Email: laferla{at}uci.edu

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 -peptide (A) and tau. Using in vitro and in vivo experiments, we report that stress-level glucocorticoid administration increases A formation by increasing steady-state levels of amyloid precursor protein (APP) and -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.

Key words: corticosterone; A peptide; Alzheimer’s disease; glucocorticoids; tau; stress

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Received April 11, 2006; accepted July 23, 2006.

Correspondence should be addressed to Frank M. LaFerla, Department of Neurobiology and Behavior, University of California, Irvine, 1109 Gillespie Neuroscience Building, Irvine, CA 92697-4545. Email: laferla{at}uci.edu

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This could be due to a reduced DHEA to cortisol ratio...

James M. Howard

J. Neurosci. Online, 21 Jun 2007 [Full text]

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