Vitamin D3 Attenuates Alzheimer's Disease-Like Pathology via Remodeling Amyloid Protein Production and Clearance Pathway in Wistar Rats.

Alzheimer's disease widely affects millions of people worldwide, accounting for 60% of dementia cases. Clinically classified by the presence of cognition impairment, pathophysiological representation includes deposited senile plaques, neurofibrillary tangles, and neuroinflammation. The pathogenesis of Alzheimer's disease (AD) remains multifaceted and is governed by multiple hypotheses. However, it undeniably involves amyloid-β (Aβ) accumulation and hyperphosphorylated tau (p-tau) pathology as the crucial events in disease initiation. Substantial evidence has correlated Vitamin D3 as a vital supplementation for the prevention of dementia and delays the progression of AD. The presence of localized Vitamin D receptors (VDR) in the brain and their capacity to convert absorbed Vitamin D to its active form have established a robust link between Vitamin D3 and Alzheimer's disease. The current study aims to explore the role of Vitamin D3 on specific parameters related to Alzheimer's disease in the Streptozotocin ICV-induced sporadic AD rat model. The study protocol included a single bilateral ICV STZ intrahippocampal injection to induce AD, followed by 21 days of treatment with two different doses of Vitamin D3 or Calcitriol (1alpha,25-dihydroxyvitamin D3)i.e., 2.5 μg/kg and 5.0 μg/kg. Results demonstrated that Vitamin D3 attenuates AD-specific parameters of amyloid plaque (Aβ1-40 and Aβ1-42), p-tau, and BACE-1. Moreover, a significant increase in the levels of both neprilysin (NEP) and insulin-degrading enzyme (IDE) was observed, both of which play a crucial role in the clearance of senile plaques. Vitamin D3 treatment also demonstrated a significant improvement in cognitive performance, along with attenuation of neuroinflammatory and oxidative stress parameters. Conclusively, optimal levels of Vitamin D3 impart neuroprotection in AD by attenuating production and increasing clearance of amyloid proteins.