title: Marginal vitamin A deficiency facilitates Alzheimer's pathogenesis.
abstract: Deposition of amyloid β protein (Aβ) to form neuritic plaques in the brain is the unique pathological hallmark of Alzheimer's disease (AD). Aβ is derived from amyloid β precursor protein (APP) by β- and γ-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 Aβ 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.
authors.affiliation: Children's Nutrition Research Center, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base for Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.|Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.|Townsend Family Laboratories, Department of Psychiatry, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Children's Nutrition Research Center, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base for Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.|Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Townsend Family Laboratories, Department of Psychiatry, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Children's Nutrition Research Center, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base for Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.|Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Children's Nutrition Research Center, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base for Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.|Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Children's Nutrition Research Center, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base for Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.|Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Hongpeng
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Townsend Family Laboratories, Department of Psychiatry, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Yili
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Children's Nutrition Research Center, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base for Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.|Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ren
authors.affiliation: Children's Nutrition Research Center, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base for Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.|Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Children's Nutrition Research Center, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base for Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. tyli@vip.sina.com.|Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. tyli@vip.sina.com.
authors.forename: Tingyu
authors.initials: T
authors.lastname: Li
authors.affiliation: Children's Nutrition Research Center, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base for Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. weihong@mail.ubc.ca.|Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. weihong@mail.ubc.ca.|Townsend Family Laboratories, Department of Psychiatry, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada. weihong@mail.ubc.ca.
authors.forename: Weihong
authors.identifier: 0000-0001-9928-889X
authors.initials: W
authors.lastname: Song
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002460:Cell Line; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007859:Learning Disabilities / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008569:Memory Disorders / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D014801:Vitamin A / Q000008:administration & dosage / Q000097:blood; D014802:Vitamin A Deficiency / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D014801:Vitamin A
keywords: Alzheimer’s disease; Amyloid β protein; Marginal vitamin A deficiency; Memory deficits; Vitamin A supplement