Many elderly individuals suffer from Alzheimer's disease (AD), which causes a growing concern. We investigated the mechanism underlying the effects of vitamin D (VD) as a prophylactic treatment. A mouse model of okadaic-acid-induced AD-like pathology was used and . Morris water maze and field trials were used to assess cognitive function. The expression levels of VDR, MTHFR, LCMT-1, PP2A, p-TAU (Thr396), and T-TAU and the methylation level of PP2A were measured by Western blotting, and a reversal of the increase in the levels of these proteins in an AD cell model was observed. We used MTHFR-knockdown SH-SY5Y cells to further test the effects of VD, treated these cells with cycloheximide and MG132, and used RT-PCR to explore the mechanism underlying MTHFR targeting. We found that the effects of VD on AD were impaired by MTHFR knockdown through a pretranscriptional mechanism. In addition, VD attenuated AD-induced cognitive impairment and significantly suppressed the expression of TAU. Our findings indicated that VD treatment alleviated TAU accumulation and rescued methylated PP2A by increasing the expression of LCMT-1 and MTHFR.
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