Journal
ACTA NEUROPATHOLOGICA
Volume 133, Issue 6, Pages 967-982Publisher
SPRINGER
DOI: 10.1007/s00401-017-1669-y
Keywords
Marginal vitamin A deficiency; Alzheimer's disease; Amyloid beta protein; Memory deficits; Vitamin A supplement
Categories
Funding
- National Natural Science Foundation of China (NSFC) [30972461, 81161120498, 81202291]
- Canadian Institutes of Health Research (CIHR) [TAD-117948]
- Alzheimer Society of Canada Postdoctoral Fellowship
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Deposition of amyloid beta protein (A beta) to form neuritic plaques in the brain is the unique pathological hallmark of Alzheimer's disease (AD). A beta is derived from amyloid beta precursor protein (APP) by beta- and gamma-secretase cleavages and turned over by glia in the central nervous system (CNS). Vitamin A deficiency (VAD) has been shown to affect cognitive functions. Marginal vitamin A deficiency (MVAD) is a serious and widespread public health problem among pregnant women and children in developing countries. However, the role of MVAD in the pathogenesis of AD remains elusive. Our study showed that MVAD is approximately twofold more prevalent than VAD in the elderly, and increased cognitive decline is positively correlated with lower VA levels. We found that MVAD, mostly prenatal MVAD, promotes beta-site APP cleaving enzyme 1 (BACE1)-mediated A beta production and neuritic plaque formation, and significantly exacerbates memory deficits in AD model mice. Supplementing a therapeutic dose of VA rescued the MVAD-induced memory deficits. Taken together, our study demonstrates that MVAD facilitates AD pathogenesis and VA supplementation improves cognitive deficits. These results suggest that VA supplementation might be a potential approach for AD prevention and treatment.
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