Graduation Year
2025
Document Type
Master's Thesis
Degree
Master of Science
Program
Biological Science
Partner Organization
Buck Institute for Research on Aging
Program Director
Patti Culross, MD, MPH
First Reader
Julie Andersen, PhD
Second Reader
Chaska Walton
Abstract
Despite FDA-approved amyloid-beta (Aβ) therapies in Alzheimer’s disease (AD), Tau pathology remains untreated and is closely linked to cognitive decline. Mitophagy, the process of mitochondrial degradation, is vital for maintaining neuronal health, and its dysregulation is implicated in AD. Recently, our lab identified a mitophagy inducing compound (MIC) that extends the lifespan of C. elegans. We hypothesized that MIC would significantly mitigate neuropathology in an AD mouse model. In this study, aged 3x-Tg AD mice were fed an MIC-containing diet, and immunohistochemistry (IHC) was performed on hippocampal tissue to visualize Aβ and phospho-Tau (pTau) lesions. While MIC had little effect on Aβ, it significantly reduced pTau, including its nuclear and perinuclear localization. These results highlight MIC as a promising candidate for treating tau pathology, addressing an unmet need in AD.