PT  - JOURNAL ARTICLE
AU  - Durk, Matthew R.
AU  - Han, Kyung
AU  - Chow, Edwin C. Y.
AU  - Ahrens, Rosemary
AU  - Henderson, Jeffrey T.
AU  - Fraser, Paul E.
AU  - Pang, K. Sandy
TI  - 1α,25-Dihydroxyvitamin D<sub>3</sub> Reduces Cerebral Amyloid-β Accumulation and Improves Cognition in Mouse Models of Alzheimer's Disease
AID  - 10.1523/JNEUROSCI.2711-13.2014
DP  - 2014 May 21
TA  - The Journal of Neuroscience
PG  - 7091--7101
VI  - 34
IP  - 21
4099  - http://www.jneurosci.org/content/34/21/7091.short
4100  - http://www.jneurosci.org/content/34/21/7091.full
SO  - J. Neurosci.2014 May 21; 34
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.