Morphological, Electrophysiological and Transcriptional Characterization of Single Neurons from Resilient and Susceptible Models of Human Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common form of dementia and accounts for a total of 60% to 80% of dementia cases. For decades, scientists have studied the underpinnings of AD by focusing on pathologies and disease pathways that result in the sickest patients. This proposal seeks to investigate AD manifestation from a different angle: instead of focusing on what causes the largest cognitive detriments, we are interested in understanding the mechanism(s) underlying how individuals who harbor AD causal mutations maintain their cognitive capabilities. Investigating genetic mechanisms associated with rare cases of individuals exhibiting cognitive resilience to AD mutations in translationally relevant models of human AD is highly likely to provide novel insight into the nature of resilience to AD-related cognitive decline that will lead to novel therapeutic strategies.