Wei “Adelyn” Tsai
Mitochondrial Gene Therapy for Resilience to Alzheimer's Pathology
Abstract
Late-onset Alzheimer’s disease (LOAD) is characterized by dementia and brain pathology. Two main risk factors of LOAD are aging and e4 allele of the apolipoprotein E (APOE) gene. However, some people with these risk factors do not develop cognitive decline or pathology and are considered being resilient. The underlying mechanisms remain unclear. Our previous work using bulk RNA sequencing data found upregulated mitochondrial NDUFV1 is linked to resilience in elderly APOE-e4 carriers. Here, we first aim to develop NDUFV1-adeno-associated virus and assess the effects of overexpressing NDUFV1 in human induced pluripotent stem cells-derived cortical neurons exposed to LOAD pathology. Second, we aim to elucidate cell specific mitochondrial mechanisms and molecules affecting resilience to LOAD pathology development and propagation. This study will contribute to the development of a new therapy and discovery of new targets leveraging mitochondria for increasing resilience to LOAD pathology.
I am very honored to receive this fellowship. This award will help move forward my thesis and enhance our understanding of how mitochondria affect resilience to Alzheimer’s disease. It is also a recognition of my ability to formulate scientific questions and conduct scientific research.
