| First Author | Durk MR | Year | 2014 |
| Journal | J Neurosci | Volume | 34 |
| Issue | 21 | Pages | 7091-101 |
| PubMed ID | 24849345 | Mgi Jnum | J:223180 |
| Mgi Id | MGI:5648168 | Doi | 10.1523/JNEUROSCI.2711-13.2014 |
| Citation | Durk MR, et al. (2014) 1alpha,25-Dihydroxyvitamin D3 reduces cerebral amyloid-beta accumulation and improves cognition in mouse models of Alzheimer's disease. J Neurosci 34(21):7091-101 |
| abstractText | We demonstrate a role of the vitamin D receptor (VDR) in reducing cerebral soluble and insoluble amyloid-beta (Abeta) peptides. Short-term treatment of two human amyloid precursor protein-expressing models, Tg2576 and TgCRND8 mice, with 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], the endogenous active ligand of VDR, resulted in higher brain P-glycoprotein (P-gp) and lower soluble Abeta 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 Abeta, 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. |
