Impact of Vitamin D on amyloid precursor protein processing and amyloid-β peptide degradation in Alzheimer's disease.

Ninety percent of the elderly population has a vitamin D hypovitaminosis, and several lines of evidence suggest that there might be a potential causal link between Alzheimer's disease (AD) and a non-sufficient supply with vitamin D. However, the mechanisms linking AD to vitamin D have not been completely understood. The aim of our study is to elucidate the impact of 25(OH) vitamin D-3 on amyloid precursor protein processing in mice and N2A cells utilizing very moderate and physiological vitamin D hypovitaminosis in the range of 20-30% compared to wild-type mice. We found that already under such mild conditions, amyloid-beta peptide (A beta) is significantly increased, which is caused by an increased beta-secretase activity and BACE1 protein level. Additionally, neprilysin (NEP) expression is downregulated resulting in a decreased NEP activity further enhancing the effect of decreased vitamin Don the A beta level. In line with the in vivo findings, corresponding effects were found with N2A cells supplemented with 25(OH) vitamin D-3. Our results further strengthen the link between AD and vitamin D-3 and suggest that supplementation of vitamin D-3 might have a beneficial effect in AD prevention. (C) 2013 S. Karger AG, Basel