Glucocorticoids Increase Amyloid-β and Tau Pathology in a Mouse Model of Alzheimer’s Disease
By K. Green, L. Billings, Benno Roozendaal, James McGaugh, F. LaFerla. Journal of Neuroscience, 2006
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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.
Subfields: Behavioral Neuroscience, Biological Psychiatry, Physiology
View Paper: https://www.semanticscholar.org/paper/5aabc657f7a409bf86c7f9e694704bbadfd02920
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Citations in the corpus
- 11β-hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action. (2013, background): “In this regard, exogenous glucocorticoids increase A and tau deposition in mouse models of Alzheimer’s disease (247), raising the intriguing possibility that the elevated cortisol levels seen in patients (688) may be more than CHAPMAN, HOLMES, AND SECKL”