Vitamin D in Alzheimer's disease: Neuroinflammatory, metabolic, and clinical implications
Mohd Kashif, Man-Hau Ho, Ashok Kumar Pandurangan, Mohammad Waseem, Dhriti Majumder, Szu-Yi ChouBackground
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. Beyond amyloid-β and tau pathology, accumulating evidence indicates that chronic neuroinflammation, oxidative stress, mitochondrial dysfunction, disrupted calcium homeostasis, and diabetes are critically contributing to disease onset and progression, underscoring the need to identify modulatory factors that influence multiple pathogenic pathways.
Objective
This review evaluates the role of vitamin D in modulating cognitive function and its association with the pathophysiology of AD.
Methods
This narrative review examines the connection between vitamin D and cognitive and neurological outcomes by integrating findings from preclinical and clinical studies. Relevant literature was identified through a PubMed search, restricted to English language publications available up to 2025.
Results
Vitamin D, a secosteroid hormone traditionally associated with bone metabolism, has emerged as a potential neuroprotective factor in the aging brain. Vitamin D receptors are widely expressed in neurons and glial cells, and vitamin D readily crosses the blood–brain barrier. Despite increasing evidence linking vitamin D deficiency to AD, its mechanistic roles in neuroinflammation and metabolic dysfunction, as well as its translational relevance, remain incompletely understood. Experimental and clinical studies suggest that vitamin D modulates amyloid metabolism, microglial activation, inflammatory signaling, redox balance, mitochondrial function, synaptic integrity, and regulates insulin resistance.
Conclusions
In this review, we integrate evidence from molecular, cellular, animal, and human studies to examine the role of vitamin D in AD. Finally, we highlight current limitations and knowledge gaps and outline future directions for clinical and translational research.