The Role of Vitamin D in Alzheimer’s Disease: A Transcriptional Regulator of Amyloidopathy and Gliopathy

• Published in: Biomedicines 2022-07, Vol.10 (8), p.1824
• Main Authors: Kang, Jiseung, Park, Mincheol, Lee, Eunkyung, Jung, Jieun, Kim, Tae
• Format: Article
• Language: English
• Subjects: Advertising executives; Alfacalcidol; Alzheimer's disease; Amine oxidase (flavin-containing); amyloidopathy; Animal cognition; Brain research; Calcifediol; Cognitive ability; Diet; Epidemiology; Ethanol; Ethylenediaminetetraacetic acid; Gene expression; Genes; Genetic aspects; Genetic transcription; gliopathy; Health aspects; Memory; memory impairment; Monoamine oxidase; mouse; Mutation; Nervous system; Neurodegeneration; Neurodegenerative diseases; Nutrient deficiency; Pathology; Phagocytosis; Proteins; Vitamin D; Vitamin deficiency
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines10081824

Alzheimer’s disease (AD) is characterized by amyloid-beta (Aβ) accumulation and cognitive mental decline. Epidemiological studies have suggested an association between low serum vitamin D levels and an increased risk of AD. Vitamin D regulates gene expression via the vitamin D receptor, a nuclear ligand-dependent transcription factor. However, the molecular mechanism underlying the pathogenic and therapeutic effects of vitamin D on AD is not fully understood yet. To better understand how vitamin D regulates the expression of genes related to AD pathology, first, we induced vitamin D deficiency in 5xFAD mice by providing a vitamin-D-deficient diet and observed the changes in the mRNA level of genes related to Aβ processing, which resulted in an increase in the Aβ load in the brain. The vitamin D-deficient diet also suppressed the expression of genes for microglial Aβ phagocytosis. Interestingly, vitamin D deficiency in the early stage of AD resulted in earlier memory impairment. In addition, we administered vitamin D intraperitoneally to 5xFAD mice with a normal diet and found lower Aβ levels with the suppressed expression of genes for Aβ generation and observed improved memory function, which may be potentially associated with reduced MAO-B expression. These findings strongly suggest the role of vitamin D as a crucial disease-modifying factor that may modulate the amyloid pathology with regard to reducing AD symptoms.