Exploring Risk Factors of Alzheimer’s Disease Using Mouse Models

<p>Mouse models of Alzheimer’s disease (AD) that accurately recapitulate pathology and molecular changes are crucial for understanding disease mechanisms and subsequent therapeutic development. We examined five commonly used mouse models of AD (5xFAD, J20, APPNL-F, APPNL-G-F, Tau P301S) and compared their whole- and phosphoproteomes with human AD (the integration of three published datasets) to study whether they can mimic protein/RNA expression discrepancies, molecular changes, and enriched pathways found in human AD cases. The mouse models especially 5xFAD and APPNL-G-F show proteomic signatures similar to human AD but lack human-specific AD progressions, such as dysregulation of synaptic pathways and networks. Integration of large-scale turnover profiling of over 10,000 proteins in 5xFAD and wild-type mice with multi-omic datasets demonstrated discordant mRNA/protein expression of amyloidome components, suggesting an interaction with β-amyloid (Aβ) may decrease protein degradation and trafficking.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biomedical Sciences

Year dc:date.available

2022

Author dc:creator

• Han, Xian

Contributors dc:contributor

• Junmin Peng, PhD

• AD mechanism
• AD mouse models
• Alzheimer's Disease
• Mouse model
• Proteomics profiling
• Splicing dysfunction
• Diseases
• Medical Molecular Biology
• Medical Sciences
• Medicine and Health Sciences
• Nervous System Diseases

Repository record dc:identifier

https://dc.uthsc.edu/dissertations/619

OAI identifier oai:identifier

oai:dc.uthsc.edu:dissertations-1619