Vitamin D basis of Alzheimer's disease: from genetics to biomarkers

Alzheimer's disease (AD) is a progressive neurodegenerative disorder seen mostly in the elderly population. While to date AD research has focused on either neurochemical disruptions, genetic studies, or the pathological hallmarks, little has been done to establish a novel approach that would encompass all three aspects, one that would overcome the current barriers in AD research and determine the cause of AD and, eventually, discover a treatment. Meanwhile, there have been strong indications in recent years that vitamin D, a secosteroid hormone, and its receptors are fundamentally involved in neurodegenerative mechanisms. Observational studies have pointed to vitamin D deficiency as a genetic risk factor for AD, Parkinson's disease (PD), vascular dementia, and multiple sclerosis (MS), as well as other neurological disorders, brought about by alterations in genes involved in metabolism, transportation, and actions of vitamin D. Molecular studies have demonstrated that vitamin D treatments prevent amyloid production while also increasing its clearance from the brain in AD. Finally, recent vitamin D intervention studies have reported significant improvement in cognitive performance in subjects with senile dementia, mild cognitive impairment, and AD. This review aims to describe how a vitamin D research strategy, fully integrating all aspects of present-day AD research, would elucidate the genetic, molecular, and biochemical background of the disease.