title: Why vitamin D in Alzheimer's disease? The hypothesis.
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.
authors.affiliation: Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Duygu
authors.initials: D
authors.lastname: Gezen-Ak
authors.affiliation: Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Selma
authors.initials: S
authors.lastname: Yılmazer
authors.affiliation: Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Erdinç
authors.initials: E
authors.lastname: Dursun
mesh_terms: D000544:Alzheimer Disease / Q000178:diet therapy* / Q000209:etiology* / Q000235:genetics; D006801:Humans; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use*; D014807:Vitamin D / Q000378:metabolism / Q000627:therapeutic use*; D014808:Vitamin D Deficiency / Q000150:complications* / Q000178:diet therapy / Q000235:genetics
chemical_list: D018696:Neuroprotective Agents; D014807:Vitamin D
keywords: 25-MARRS; Alzheimer's disease; ERp57/1; VDR; amyloid-β; calcium homeostasis; haplotype; hormone imbalance; oxidative stress; vitamin D; vitamin D deficiency