Acta Neuropathologica

, Volume 133, Issue 6, pp 967–982 | Cite as

Marginal vitamin A deficiency facilitates Alzheimer’s pathogenesis

  • Jiaying Zeng
  • Li Chen
  • Zhe Wang
  • Qian Chen
  • Zhen Fan
  • Hongpeng Jiang
  • Yili Wu
  • Lan Ren
  • Jie Chen
  • Tingyu LiEmail author
  • Weihong SongEmail author
Original Paper


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.


Marginal vitamin A deficiency Alzheimer’s disease Amyloid β protein Memory deficits Vitamin A supplement 



Alzheimer’s disease

Amyloid β protein


Amyloid β precursor protein


Marginal vitamin A deficiency



This work was supported by grants from the National Natural Science Foundation of China (NSFC) Grant 30972461, 81161120498 (TL), and 81202291 (LC), and Canadian Institutes of Health Research (CIHR) Grant TAD-117948 (WS). WS is the holder of the Tier 1 Canada Research Chair in Alzheimer’s Disease. ZW is supported by the Alzheimer Society of Canada Postdoctoral Fellowship.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

401_2017_1669_MOESM1_ESM.docx (171 kb)
Supplementary material 1 (DOCX 170 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.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 DisordersChildren’s Hospital of Chongqing Medical UniversityChongqingChina
  2. 2.Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqingChina
  3. 3.Townsend Family Laboratories, Department of PsychiatryThe University of British ColumbiaVancouverCanada

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