The aim of this study was to explore the preventive and curative effect and mechanisms of Acer truncatum Bunge seed oil (ASO) on Alzheimer’s disease using 5×FAD transgenic mice as an animal model.

1-month-old male 5×FAD transgenic mice were randomly selected and fed a standard diet supplemented with 4% ASO for 5 months (AD+ASO group), Male wild type control group (WT group) and a 5×FAD transgenic Alzheimer’s disease model group (AD group) were also included. Before sampling, animal behavioral experiments such as Barnes maze and elevated plus maze were conducted, followed by immunofluorescence staining of the hippocampus and cerebral cortex, high-throughput 16S rRNA sequencing, and bioinformatics analysis of gut microbiota.

Behavioral results showed that ASO intervention could improve the spatial learning and memory and ameliorate cognitive impairment of 5×FAD transgenic mice. Immunofluorescence histological results showed that ASO reduced the deposition of neuroinflammatory plaques formed by beta-amyloid peptide (Aβ) accumulation in the hippocampus and cerebral cortex by inhibiting the formation of amyloid plaques. ASO supplementation increased level of the antioxidant enzyme-glutathione peroxidase (GSH-Px) in the hippocampal tissue of AD mice, which in turn increased the body's antioxidant capacity. Bioinformatics results showed that the ASO could improve the richness and diversity of the gut microbiota in AD mice and play a positive role in regulating the gut microbiota.

ASO can inhibit the formation of Aβ amyloid plaques by regulating the structure and abundance of gut microbiota, improve the learning and memory of AD mice and exert its neuroprotective effect, provides new materials and possibilities for protection of AD.