iTRAQ-Based Proteomic Analysis of APP Transgenic Mouse Urine Exosomes

• Published in: International journal of molecular sciences Vol. 24; no. 1; p. 672
• Main Authors: Zhou, Xiaojing, Sheikh, Abdullah Md, Matsumoto, Ken-Ichi, Mitaki, Shingo, Shibly, Abu Zaffar, Zhang, Yuchi, A, Garu, Yano, Shozo, Nagai, Atsushi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 30.12.2022; MDPI AG
• Subjects: Alzheimer’s disease; amyloid beta; iTRAQ; proteomic analysis; urine exosomes; iTRAQ; Alzheimer’s disease; urine exosomes; amyloid beta; proteomic analysis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24010672

Alzheimer's disease (AD) is a common dementia disease in the elderly. To get a better understanding of the pathophysiology, we performed a proteomic analysis of the urine exosomes (U-exo) in AD model mice (J20). The polymer precipitation method was used to isolate U-exo from the urine of 3-month-old J20 and wild-type (WT) mice. Neuron-derived exosome (N-exo) was isolated from U-exo by immunoprecipitation. iTRAQ-based MALDI TOF MS/MS was used for proteomic analysis. The results showed that compared to WT, the levels of 61 and 92 proteins were increased in the J20 U-exo and N-exo, respectively. Gene ontology enrichment analysis demonstrated that the sphingolipid catabolic process, ceramide catabolic process, membrane lipid catabolic process, Aβ clearance, and Aβ metabolic process were highly enriched in U-exo and N-exo. Among these, Asah1 was shown to be the key protein in lipid metabolism, and clusterin, A , neprilysin, and ACE were related to Aβ metabolism and clearance. Furthermore, protein-protein interaction analysis identified four protein complexes where clusterin and A participated as partner proteins. Thus, J20 U-exo and N-exo contain proteins related to lipid- and Aβ-metabolism in the early stages of AD, providing a new insight into the underlying pathological mechanism of early AD.