Abstract: Abstract: Objective To explore the key cytological mechanism of Alzheimer’s disease in SAMP8 mice. Methods Two-month-old and 8-month-old SAMP8 mice were used as the accelerated-aging model of dementia, and 40 SAMR1 mice at the same age were used as the control group. The lipid rafts of hippocampus were extracted from young and adult mice for analysis using high performance liquid chromatography-tandern mass spectrometry (HPLC-MS/MS). The lipid raft proteome data were introduced into DAVID bioinformatics analysis tool, then Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out. The results of bioinformatics analysis were verified by mitochondrial membrane potential and Morris water maze analysis. Results Compared with the control mice of SAMR1, the aged SAMP8 mice showed obvious cognitive impairment. GO analysis showed that the mitochondrial-related proteins decreased greatly in aged SAMP8 mice. KEGG analysis showed that the oxidative phosphorylation of mitochondria was greatly reduced in the hippocampus of SAMP8 mice. Mitochondrial membrane potential analysis showed that the mitochondrial membrane potential decreased significantly in the hippocampus of aged SAMP8 mice. Conclusion During aging, the most critical cellular change in hippocampus is the excessive decline of mitochondrial oxidative phosphorylation, which may be an important cellular mechanism of dementia in SAMP8 mice.

Key words: Alzheimer disease, aging, premature, cell aging, oxidative phosphorylation, mitochondria