Proteomic alterations in the cortex and hippocampus of APP/PS1 mice: insights into potential mechanisms of Alzheimer's disease

doi:10.5246/jcps.2025.05.034

Abstract

Abstract:

Alzheimer's disease (AD) stands as the principal cause of dementia globally, influenced by myriad risk factors. Despite extensive research, the pathogenesis of AD remains elusive. This study aimed to identify differentially expressed proteins in the cortex and hippocampus that are associated with AD. Our comparative analysis revealed significant impairments in spatial memory, cognitive function, and mobility in APPswe/PSEN1dE9 (APP/PS1) mice. Proteomic analysis of cortex tissues revealed 6405 proteins, with 283 showing significant alterations. In the hippocampus, 5574 proteins were identified, among which 244 were significantly altered, suggesting a connection to AD pathology. Through bioinformatics, functional analysis, and protein-protein interaction (PPI) network mapping, we demonstrated that AD progression in the cortex was predominantly driven by inflammation-related pathways, including neutrophil extracellular trap formation, as well as complement and coagulation cascades. Additionally, PPI analysis linked AD progression in the cortex to ribosome-associated proteins. Moreover, several proteins, including APP, IDE, SDHB, and RB1CC1, exhibited alterations in both the cortex and hippocampus. These findings offered novel insights into the diagnostics and therapeutic strategies for AD.

Key words: Alzheimer's disease, Proteomic, Cortex, Hippocampus, APPswe/PSEN1dE9

Supporting:

Hongyan Yin, Sihan You, Jiayi Zhang, Luyao Sun, Jinmeng Cao, Xinxing Liu, Shuang Li, Chunyan Guo. Proteomic alterations in the cortex and hippocampus of APP/PS1 mice: insights into potential mechanisms of Alzheimer's disease[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(5): 443-457.

Figures/Tables 10

References 36

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