Date of Award
12-2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Program
Biomedical Sciences
Track
Genetics, Genomics & Informatics
Research Advisor
Junmin Peng, PhD
Committee
Young-Goo Han, PhD; Qian Li, PhD; Lindsay Scwarz, PhD; Ansley Grimes Stanfill, Ph.D, R.N., F.A.A.N.; Gang Wu, PhD
Keywords
Alzheimer;biomarker;LBD;multi-omics;Proteomics;serum
Abstract
Amyloid pathology is the central hallmark of Alzheimer’s disease (AD) and related dementias (ADRD). We analyzed the dementia with Lewy bodies disease (DLBD) proteome, a disorder also associated with amyloid pathology, and compared to the AD proteome, identifying conserved alterations in amyloid pathology and shared components in amyloid plaques, including MDK and NTN1. We additionally evaluated major AD mouse models to determine their relevance to human disease and identify shared proteomic alterations. We observed alterations in several highly conserved matrisomal components consistently im- plicated in proteomic analyses of human amyloidosis disorders. We additionally identified several pathways influenced by amyloid-pathology that were consistently shared between human AD and the 5xFAD and APPNL-G-F mouse models, including amyloid regulation, nitric oxide regulation, superoxide regulation, cell, adhesion, and cellular component organization. Finally, we investigated global proteome turnover changes in 5xFAD mice to shed light on the discrepancy between transcriptome and proteome in AD. We achieved un- precedented quantitation of protein half-lives in mice and identified decreased turnover in key amyloidome components such as APOE. Our results indicate our proteomics workflow can serve as a powerful resource for studying fundamental protein turnover, interrogating biological questions, and developing therapeutics for neurodegenerative disorders.
ORCID
0000-0003-1793-5630
DOI
10.21007/etd.cghs.2023.0643
Recommended Citation
Yarbro, Jay M. (0000-0003-1793-5630), "A Multi-Faceted Approach to the Alzheimer’s Disease Proteome: From Human to Mouse Models" (2023). Theses and Dissertations (ETD). Paper 659. http://dx.doi.org/10.21007/etd.cghs.2023.0643.
https://dc.uthsc.edu/dissertations/659