Date of Award

12-2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program

Biomedical Sciences

Track

Cancer and Developmental Biology

Research Advisor

Junmin Peng, PhD

Committee

Xinwei Cao, PhD; Hongbo Chi, PhD; Shondra Pruett-Miller, PhD; Megan K. Mulligan, PhD; Stanislav S. Zakharenko, PhD

Keywords

AD mechanism, AD mouse models, Alzheimer's Disease, Mouse model, Proteomics profiling, Splicing dysfunction

Abstract

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.

Declaration of Authorship

Declaration of Authorship is included in the supplemental files.

ORCID

https://orcid.org/0000-0002-3802-6420

DOI

10.21007/etd.cghs.2022.0606

Additional Files
2022-024-Han-DOA.pfd.pdf (256 kB)
Declaration of Authorship
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