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Abstract. Grape seed proanthocyanidin (GSPA) consists of catechin, epicatechin and epicatechin gallate, which are strong antioxidants that are beneficial to health and may attenuate or prevent Alzheimer's disease (AD). In the present study, the effects of GSPA on pheochromocytoma (PC12) cell viability were determined using cell counting kit-8 and lactate dehydrogenase (LDH) assays, whereas apoptosis and mitochondrial membrane potential (ψm) were measured via low cytometry analysis. The effect of GSPA administration on the behavior and memory of amyloid precursor protein (APP)/presenilin-1 (PS-1) double transgenic mice was assessed using a Morris water maze. APP Aβ peptides and tau hyperphosphorylation were examined by western blotting; whereas the expression levels of PS-1 were evaluated by reverse transcription-quantitative polymerase chain reaction and compared with pathological sections stained with hematoxylin-eosin and Congo red. Data from the in vitro experiments demonstrated that GSPA significantly alleviated Aβ25-35 cytotoxicity and LDH leakage ratio, inhibited apoptosis and increased ψm. The findings from the in vivo experiments showed a significant enhancement in cognition and spatial memory ability, an improvement in the pathology of APP and tau protein and a decrease in PS-1 mRNA expression levels. Therefore, the results of the present study indicated that GSPA may be a novel therapeutic strategy for the treatment of AD or may, at the very least, improve the quality of life of patients with AD. [ABSTRACT FROM AUTHOR]