RT Journal Article
SR Electronic
T1 1α,25-Dihydroxyvitamin D<sub>3</sub> Reduces Cerebral Amyloid-β Accumulation and Improves Cognition in Mouse Models of Alzheimer's Disease
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7091
OP 7101
DO 10.1523/JNEUROSCI.2711-13.2014
VO 34
IS 21
A1 Durk, Matthew R.
A1 Han, Kyung
A1 Chow, Edwin C. Y.
A1 Ahrens, Rosemary
A1 Henderson, Jeffrey T.
A1 Fraser, Paul E.
A1 Pang, K. Sandy
YR 2014
UL http://www.jneurosci.org/content/34/21/7091.abstract
AB We demonstrate a role of the vitamin D receptor (VDR) in reducing cerebral soluble and insoluble amyloid-β (Aβ) peptides. Short-term treatment of two human amyloid precursor protein-expressing models, Tg2576 and TgCRND8 mice, with 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], the endogenous active ligand of VDR, resulted in higher brain P-glycoprotein (P-gp) and lower soluble Aβ levels, effects negated with coadministration of elacridar, a P-gp inhibitor. Long-term treatment of TgCRND8 mice with 1,25(OH)2D3 during the period of plaque formation reduced soluble and insoluble plaque-associated Aβ, particularly in the hippocampus in which the VDR is abundant and P-gp induction is greatest after 1,25(OH)2D3 treatment, and this led to improved conditioned fear memory. In mice fed a vitamin D-deficient diet, lower cerebral P-gp expression was observed, but levels were restored on replenishment with VDR ligands. The composite data suggest that the VDR is an important therapeutic target in the prevention and treatment of Alzheimer's disease.