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Neurobiol Aging. 2012 Aug;33(8):1844.e1-9. doi: 10.1016/j.neurobiolaging.2011.12.038. Epub 2012 Feb 4.

Vitamin D receptor and Alzheimer's disease: a genetic and functional study.

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Hussman Institute for Human Genomics, University of Miami Miller School of Medicine 1501 NW 10 Ave, Miami, Florida, USA.


Genetic studies on late-onset Alzheimer's disease (AD) have repeatedly mapped susceptibility loci onto chromosome 12q13, encompassing the vitamin D receptor (VDR) gene. Epidemiology studies have indicated vitamin D insufficiency as a risk factor for AD. Given that VDR is the major mediator for vitamin D's actions, we sought to clarify the role of VDR in late-onset AD. We conducted an association study in 492 late-onset AD cases and 496 controls with 80 tagging single nucleotide polymorphisms (SNPs). The strongest association was found at a promoter SNP rs11568820 (P = 9.1 × 10(-6), odds ratio (OR) = 1.69), which resides within the transcription factor Cdx-2 binding site and the SNP has been also known as CDX2. The risk-allele at rs11568820 is associated with lower VDR promoter activity (p < 10(-11)). The overexpression of VDR or vitamin D treatment suppressed amyloid precursor protein (APP) transcription in neuroblastoma cells (p < 0.001). We provide both statistical evidence and functional data suggesting VDR confers genetic risk for AD. Our findings are consistent with epidemiology studies suggesting that vitamin D insufficiency increases the risk of developing AD.

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