Date of Award
2024
Document Type
Dissertation
Publication Status
Version of Record
Submission Date
October 2026
Thesis/Dissertation Advisor [Chair]
Wu, Jang-Yen
Abstract
Alzheimer's disease (AD) is projected to triple by 2050, highlighting the urgent need for disease-modifying treatment strategies. Our gene therapy approach tackles three critical challenges: a) delivering drugs effectively to the brain and brain bioavailability of those delivered drugs, b) intervening early in the disease process to prevent progression into nonreversible stages, and c) managing the behavioral and psychological symptoms of dementia (BPSD) that significantly impact patients and caregivers. Our non-invasive ocular delivery system effectively delivered therapies to CNS as indicated by the localization of those transcribed genes and translated protein products in different brain regions, including the hippocampus, cortex, dorsal lateral geniculate nucleus, red nucleus, and pontine nucleus This approach could overcome the limitations of traditional drug delivery methods for neurological diseases. In a 3xTg AD mouse model of AD, we evaluated the efficacy of Choline Acetyltransferase (ChAT) gene therapy on early disease progression. A single treatment improved impaired memory functions such as cognitive flexibility, memory extinction and working memory, reduced amyloid beta oligomers and phosphorylated tau protein levels, and enhanced mitochondrial dynamics through the regulation of fusion, fission and mitophagy. Additionally, ChAT gene therapy modulated apoptosis, inflammation and the activity of microglia and astrocytes in parts through the activation of AKT. These findings suggest ChAT gene therapy's potential to slow or prevent AD progression if administered early in the disease course.
Extent
202 p.
Recommended Citation
Bhandari, Subash, "MULTIMODAL THERAPIES FOR ALZHEIMER’S DISEASE" (2024). Electronic Theses and Dissertations 2020 - Present. 1462.
https://digitalcommons.fau.edu/etd_general/1462
Identifier
FA00014400
Comments
Includes bibliography.|Dissertation (PhD)--Florida Atlantic University, 2024.|FAU Electronic Theses and Dissertations Collection|Includes bibliography.