Developing hippocampal delivery of AAV-NeuroD1 as a novel therapy for Alzheimer's disease

Open Access
Author:
Wang, Fan
Graduate Program:
Molecular, Cellular and Integrative Biosciences
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
December 02, 2015
Committee Members:
  • Gong Chen, Thesis Advisor
  • Bernhard Luscher, Thesis Advisor
  • Richard W Ordway, Thesis Advisor
  • Yingwei Mao, Thesis Advisor
Keywords:
  • Alzheimer's disease
  • NeuroD1
  • hippocampus
  • AAV
Abstract:
Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the elderly and is the leading cause of most dementia cases. Patients with AD experience gradual loss of cognitive abilities. Reactive astrogliosis is one of the most well-known features of AD pathology. Here, we are using a widely used 5xFAD mouse model to study NeuroD1 effect in AD. After hippocampal delivery of AAV-NeuroD1, we observed a significant reduction of reactive astrogliosis in the hippocampus region by testing several markers such as GFAP, S100β, GLT-1, and Sox2. We also detected changes in calretinin+ neuronal projections and blood vessel distributions by CD31 staining. More excitingly, we were able to see an improvement of learning and memory by conducting a novel-object recognition test 1 month after NeuroD1 delivery. These results suggest a potential novel gene therapy for AD using NeuroD1 as a single factor. Besides, we also injected Aβ oligomers into the hippocampus as an alternative AD model which recapitulate neuronal loss in AD patients.