Abstract

Background and Objectives: Alzheimer’s disease (AD) is the most prevalent form of dementia in older individuals. Ferroptosis, a programmed cell death characterized by iron-dependent membrane lipid peroxidation is implicated in AD pathology. Increasing evidences have shown that plant-derived dietary antioxidants exhibit their anti-ferroptosis activity. However, the anti-AD mechanism of plant-derived dietary antioxidants remains elusive. Therefore, this review aims to explore the anti-AD effects of plant-derived dietary antioxidants via ferroptosis regulation. Methods and Study Design: This review examines the available published data from all peer-reviewed original research articles on following topics: ferroptosis mechanisms, the role of ferroptosis in AD, the preclinical or clinical studies of plant-derived dietary antioxidants in cell, animal models of AD or patients with AD. Results: Ferroptosis is involved in AD pathology. Importantly, we clarify why docosahexaenoic acid (DHA)-rich brain phospholipids are extremely susceptible to lipid peroxidation. In addition, plant-derived dietary antioxidants such as vitamin E (VE), resveratrol, epigallocatechin-3-gallate (EGCG), curcumin, quercetin, baicalein and alpha-lipoic acid (ALA) show the anti-AD effects in preclinical AD models and prevent decline of cognition in healthy elderly population. Clinical studies show that ALA prevents decline of cognition of AD patients although most plant-derived dietary antioxidants exhibit conflicting results. Conclusions: It suggests that a plant-based diet may lead to potential health benefits in preventing cognitive decline in healthy elderly population. In regard to ALA, further clinical studies are highly recommended to evaluate its therapeutic potential that could optimize its dietary intake for preventing and alleviating decline of cognition of patients with AD.

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