Background: Although clinical vitamin A deficiency (VAD), which is a public health problem developing throughout the world, has been well controlled, marginal vitamin A deficiency (MVAD) is far more prevalent, especially among pregnant women and preschool children in China. Increasing evidence suggests that VAD is involved in the pathogenesis of Alzheimer’s disease (AD). However, whether MVAD, beginning early in life, increases the risk of developing AD has yet to be determined.Objective: The goal of this study was to investigate the long-term effects of MVAD on the pathogenesis of AD in rats. Method: An MVAD model was generated from maternal MVAD rats and maintained with an MVAD diet after weaning. The males were bilaterally injected with aggregated amyloid β (Aβ)1–42 into the CA3 area of the hippocampus, and the AD-associated cognitive and neuropathological phenotypes were examined. Results: We found that MVAD feeding significantly aggravated Aβ1-42-induced learning and memory deficits in the Morris water maze test. MVAD did not induce the mRNA expression of retinoic acid receptors (RARs), a disintegrin and metalloprotease 10 (ADAM10) or insulin-degrading enzyme (IDE) in Aβ1-42-injected rats. Moreover, RARα and RARγ mRNA were positively correlated with ADAM10 mRNA, whereas RARβ mRNA was positively correlated with IDE mRNA. Conclusion: Our study suggests that MVAD beginning from the embryonic period perturbs the ADassociated genes, resulting in an enhanced risk of developing AD.