Quantitative Proteomic Analysis of APP/PS1 Transgenic Mice

Jiayuan Wang; Xinyu Wang; Zihui An; Xuan Wang; Yaru Wang; Yuehan Lu; Mengsheng Qiu; Zheqi Liu; Zhou Tan

doi:10.2174/0115672050345431241113112608

Quantitative Proteomic Analysis of APP/PS1 Transgenic Mice

Curr Alzheimer Res. 2024 Dec 2. doi: 10.2174/0115672050345431241113112608. Online ahead of print.

Authors

Jiayuan Wang¹, Xinyu Wang¹, Zihui An¹, Xuan Wang¹, Yaru Wang¹, Yuehan Lu¹, Mengsheng Qiu¹, Zheqi Liu², Zhou Tan¹

Affiliations

¹ Zhejiang Key Laboratory of Organ Development and Regeneration, School of Life and Environmental Science, Hangzhou Normal University, Hangzhou311121, China.
² Zhejiang Chinese Medical University, Hangzhou TCM Hospital, Hangzhou, 311121, China.

PMID: 39623717
DOI: 10.2174/0115672050345431241113112608

Abstract

Background: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting the central nervous system (CNS), with its etiology still shrouded in uncertainty. The interplay of extracellular amyloid-β (Aβ) deposition, intracellular neurofibrillary tangles (NFTs) composed of tau protein, cholinergic neuronal impairment, and other pathogenic factors is implicated in the progression of AD.

Objective: The current study endeavors to delineate the proteomic landscape alterations in the hippocampus of an AD murine model, utilizing proteomic analysis to identify key physiological and pathological shifts induced by the disease. This endeavor aims to shed light on the underlying pathogenic mechanisms, which could facilitate early diagnosis and pave the way for novel therapeutic interventions for AD.

Methods: To dissect the proteomic perturbations induced by Aβ and Presenilin-1 (PS1) in the AD pathogenesis, we undertook a label-free quantitative (LFQ) proteomic analysis focusing on the hippocampal proteome of the APP/PS1 transgenic mouse model. Employing a multi-faceted approach that included differential protein functional enrichment, cluster analysis, and protein-protein interaction (PPI) network analysis, we conducted a comprehensive comparative proteomic study between APP/PS1 transgenic mice and their wild-type C57BL/6 counterparts.

Results: Mass spectrometry identified a total of 4817 proteins in the samples, with 2762 proteins being quantifiable. Comparative analysis revealed 396 proteins with differential expression between the APP/PS1 and control groups. Notably, 35 proteins exhibited consistent temporal regulation trends in the hippocampus, with concomitant alterations in biological pathways and PPI networks.

Conclusions: This study presents a comparative proteomic profile of transgenic (APP/PS1) and wild-type mice, highlighting the proteomic divergences. Furthermore, it charts the trajectory of proteomic changes in the AD mouse model across the developmental stages from 2 to 12 months, providing insights into the physiological and pathological implications of the disease-associated genetic mutations.

Keywords: APP/PS1; Alzheimer's disease; ferroptosis.; hippocampus; mitophagy; proteomics.