Proteomic Profiles of the Early Mitochondrial Changes in APP/PS1 and ApoE4 Transgenic Mice Models of Alzheimer's Disease

Alzheimer's disease (AD) is one of the most common progressive neurodegenerative diseases. Apolipoprotein E4 (ApoE4) carriers account for 40% of all AD cases, emphasizing the importance of ApoE4 in the pathogenesis of AD. In the present study, we explored the changes of hippocampal proteins expression profile at the early stage (3 month-old) of APP/PS1 and ApoE4 knockin mice with the aim to find potential key pathways involved in AD progression. Proteomic analysis showed a lot of differentially expressed proteins (DEPs), 247 (137 increased and 110 decreased) and 1125 (642 increased and 484 decreased) in the hippocampus of APP/PS1 and ApoE4 mice, respectively, compared with the wild-type (WT) mice, using a cutoff of 1.2-fold change. Functional classification of DEPs revealed that these proteins mainly comprise proteins involved in acetylation, methylation, endocytosis/exocytosis, chaperone, oxidoreductase, mitochondrial, cytoskeletal, and synaptic proteins in APP/PS1 mice compared with the WT mice. Likewise in ApoE4 mice compared with the WT mice, the DEPs are mostly involved in the functions of synapses, ribosomes, mitochondria, spliceosomes, endocytosis/exocytosis, oxidative phosphorylation, and proteasomes. STRING analysis suggested that some DEPs were involved in insulin signaling and mitochondria! electron transport chain in the two mouse models. The abnormal changes of insulin signaling and mitochondrial electron transport chain were further verified by Western blot. Taken together, our study exposed the changes of hippocampal protein expression profiles at the early stage of APP/PS1 and ApoE4 knockin mice, and the change of insulin signaling and mitochondrial electron transport chain may be the key molecular processes involved in AD progression.