Alzheimer’s disease (AD) is the most prevalent type of dementia, marked by severe memory loss and cognitive decline, for which there is currently no cure or effective treatment. While our understanding of the mechanisms underlying the pathobiology of AD is rapidly growing, much less is known about the neural mechanisms that give rise to non-cognitive symptoms of dementia such as psychosis, depression, agitation, and aggression. Nevertheless, non-cognitive symptoms of dementia significantly impact the quality of life of patients and importantly of their caregivers. Effective therapies for managing these symptoms are lacking, or are often associated with increased mortality in demented patients. As an independent investigator, I will launch a research program to elucidate neural substrates of non-cognitive symptoms of AD. In this arm of my research program, I will leverage single-cell technologies to profile postmortem human brains with patient-derived in vitro models for mechanistic studies. I am particularly eager to leverage my expertise in neuronal-glial interactions to dissect the pathophysiological role of hyperexcitable circuits and altered neurochemicals onto glial metabolic function in the etiology of neuropsychiatric symptoms of Alzheimer’s disease.
