Why Vitamin D in Alzheimer's Disease? The Hypothesis


Gezen-Ak D. , Yilmazer S. , Dursun E.

JOURNAL OF ALZHEIMERS DISEASE, vol.40, no.2, pp.257-269, 2014 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 40 Issue: 2
  • Publication Date: 2014
  • Doi Number: 10.3233/jad-131970
  • Title of Journal : JOURNAL OF ALZHEIMERS DISEASE
  • Page Numbers: pp.257-269
  • Keywords: Alzheimer's disease, amyloid-beta, calcium homeostasis, ERp57/1, 25-MARRS, haplotype, hormone imbalance, oxidative stress, VDR, vitamin D, vitamin D deficiency, D-RECEPTOR GENE, NERVE GROWTH-FACTOR, NITRIC-OXIDE SYNTHASE, AMYLOID BETA-PEPTIDE, 1,25-DIHYDROXYVITAMIN D-3, CEREBROSPINAL-FLUID, 1-ALPHA,25-DIHYDROXYVITAMIN D-3, CALCIUM-CHANNEL, D DEFICIENCY, D HORMONE

Abstract

Scientists have worked for over a century to uncover the basis of Alzheimer's disease (AD) with the ultimate goal of discovering a treatment. However, none of the approaches utilized have defined the exact cause of the disease or an ultimate treatment for AD. In this review, we aim to define the role of vitamin D in AD from a novel and fundamental perspective and attempt to answer the following question: Why should we seriously consider "simple" vitamin D as a "fundamental factor" in AD? To answer this question, we explain the protective effects of vitamin D in the central nervous system and how the action of vitamin D and AD-type pathology overlap. Furthermore, we suggest that the role of vitamin D in AD includes not only vitamin D deficiency and vitamin D-related genes but also the disruption of vitamin D metabolism and action. This suggestion is supported by evidence that the disruption of vitamin D pathways mimic amyloid pathology. We define the term "inefficient utilization of vitamin D" as any alteration in vitamin D-related genes, including receptors, the enzymes related to vitamin D metabolism or the transporters of vitamin D, and we discuss the potential correlation of vitamin D status with the vulnerability of neurons to aging and neurodegeneration. Finally, in addition to the current knowledge that defines AD, we suggest that AD could be the result of a long-term hormonal imbalance in which the critical hormone is vitamin D, a secosteroid that has long been misnamed.