Why vitamin D in Alzheimer's disease? The hypothesis

• Published in: Journal of Alzheimer's disease Vol. 40; no. 2; p. 257
• Main Authors: Gezen-Ak, Duygu, Yılmazer, Selma, Dursun, Erdinç
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2014
• Subjects: Alzheimer Disease - diet therapy; Alzheimer Disease - etiology; Alzheimer Disease - genetics; Humans; Neuroprotective Agents - metabolism; Neuroprotective Agents - therapeutic use; Vitamin D - metabolism; Vitamin D - therapeutic use; Vitamin D Deficiency - complications; Vitamin D Deficiency - diet therapy; Vitamin D Deficiency - genetics; hormone imbalance; haplotype; VDR; vitamin D; amyloid-β; ERp57/1; calcium homeostasis; Alzheimer's disease; oxidative stress; vitamin D deficiency; 25-MARRS
• ISSN: 1875-8908
• DOI: 10.3233/JAD-131970

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.