PT  - JOURNAL ARTICLE
AU  - Kim N. Green
AU  - Lauren M. Billings
AU  - Benno Roozendaal
AU  - James L. McGaugh
AU  - Frank M. LaFerla
TI  - Glucocorticoids Increase Amyloid-β and Tau Pathology in a Mouse Model of Alzheimer’s Disease
AID  - 10.1523/JNEUROSCI.2797-06.2006
DP  - 2006 Aug 30
TA  - The Journal of Neuroscience
PG  - 9047--9056
VI  - 26
IP  - 35
4099  - http://www.jneurosci.org/content/26/35/9047.short
4100  - http://www.jneurosci.org/content/26/35/9047.full
SO  - J. Neurosci.2006 Aug 30; 26
AB  - 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 β-peptide (Aβ) and tau. Using in vitro and in vivo experiments, we report that stress-level glucocorticoid administration increases Aβ formation by increasing steady-state levels of amyloid precursor protein (APP) and β-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.