**1. Introduction**

Recently, involvement of Vitamin D (V-D) in cognitive impairment is reported.

V-D is a secosteroid and occurs in two distinctive major forms: Vitamin D2 (V-D2) and Vitamin D3 (V-D3). V-D3 is a 27-carbon derivative of cholesterol, and V-D2 is a 28-carbon derivative from plant ergosterol. The structure of V-D2 differs from V-D3 by containing an extra methyl group and a double bond between carbon 22 and 23 (**Figure 1**). Both V-D derivatives appear to have

© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

similar biological effects in humans [1, 2]. V-D3 is about four times as potent as V-D2 [3]. Interestingly, V-D2 is a naturally occurring V-D form derived from a fat extract of yeast by the exposure to UV light, and the metabolites were not detectable in the blood of vertebrates such as humans, unless administered from an external source [3, 4]. Thus, V-D2 is not synthesized in vivo and is regarded as a supplement. The metabolites derived from V-D2 are not equivalent to those for V-D3 [5]. In contrast to V-D2, V-D3 is the naturally synthesized within the skin and oils of fur. Although both microsomal and mitochondrial 25-hydroxylases act on V-D3, they do not act on V-D2 [4, 6, 7], and furthermore the V-D binding protein shows lower affinity for V-D2 than V-D3 and its metabolites [8]. Currently, clinical applications of V-D for immunosuppression and reduction of pro-inflammatory immune pathways demonstrate that V-D is a prosteroid hormone rather than a vitamin [9, 10]. V-D cross blood-brain barrier by passive diffusion and enter the cerebrospinal fluid and brain. The beneficial effects in reducing the relapse risk in multiple sclerosis through its immune-regulatory effects were reported [11].

**Figure 1.** Structural differences between Vitamin D2 and Vitamin D3.

Recent epidemiologic studies report V-D3 deficiency as a risk factor of cardiovascular disease including cardiac hypertrophy, myocardial remodeling developed to heart failure (HF) [12, 13] and some prospective studies report the relationship between hypovitaminosis-D and an increased risk of cognitive decline in elderly population [14] and suggested that supplementation of V-D could prevent the cognitive disorders [15–17], and its effects for the clearance of aggregated amyloid-β (Aβ) in AD brain [18].

In this chapter, we present the different binding affinity of V-D2 and V-D3 to amyloidogenic protein in brain: Aβ and prion protein.
