Cellular and Molecular Mechanisms of Vitamin D Deficiency in Aging and Alzheimer’s Disease

Vitamin D is implicated in regulation of various biological processes, including calcium homeostasis, neurogenesis, synaptic plasticity, the immune system, and inflammation. Nowadays, most part of the population worldwide is affected by vitamin D deficiency. The decreases in different factors, including the cutaneous thickness, the sun exposure time, muscle mass, kidney efficiency, and sex steroids in aged people (especially women), as well as malnutrition cause vitamin D deficiency, which in turn may act as an important risk factor for Alzheimer’s disease (AD). There is a reciprocal relationship between amyloid β (Aβ) as a core factor that initiates the onset and progression of AD and the increases in calcium (Ca2+) levels in neurons. Vitamin D via genomic functions, including either a decreasing expression of L-type Ca2+ channels or increasing expression of Ca2+ pumps, Na+/Ca2+ exchanger, as well as Ca2+ buffers, has the main role in Ca2+ homeostasis. Therefore, vitamin D through influencing intracellular Ca2+ can prevent Aβ production and inhibit its subsequent neurotoxic effects. It also indirectly controls neuroinflammation and oxidative stress via influencing intracellular Ca2+ levels and thereby postpone either onset or progress of AD.

Taken together, this review shows that vitamin D can control the normal process of physiological aging, and its deficiency may initiate AD by disrupting different cellular and molecular mechanisms in the neural system. Therefore, vitamin D as a food and drug supplement along with other effective drugs may have a preventive role in the induction and progression of AD.