Date of Award
Doctor of Philosophy (PhD)
Cancer and Developmental Biology
Junmin Peng, PhD
Xinwei Cao, PhD; Hongbo Chi, PhD; Shondra Pruett-Miller, PhD; Megan K. Mulligan, PhD; Stanislav S. Zakharenko, PhD
AD mechanism, AD mouse models, Alzheimer's Disease, Mouse model, Proteomics profiling, Splicing dysfunction
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.
Han, Xian (https://orcid.org/0000-0002-3802-6420), "Exploring Risk Factors of Alzheimer’s Disease Using Mouse Models" (2022). Theses and Dissertations (ETD). Paper 619. http://dx.doi.org/10.21007/etd.cghs.2022.0606.
Available for download on Friday, January 10, 2025