Dysregulation of pH dynamics in Alzheimer Disease Pathogenesis

Alzheimer’s disease results in the accumulation of characteristic plaques and tangles: collections of proteins in the brain that cannot be dissolved. It is unknown why neurons fail to clean up these so-called “garbage” proteins, and why this risk of failure increases with age. This research will focus on a “pH hypothesis,” which suggests that impaired regulation of cellular pH promotes neuronal dysfunction and death in Alzheimer’s disease by preventing protein clearance and promoting protein aggregation. This understudied area is key to fully understanding the biology of Alzheimer’s disease, and may lead to critical and complementary therapeutic strategies aimed at preventing or curing the disease.

Affiliated Investigators

Aimee Kao, Ph.D.

University of California, San Francisco

Dr. Aimee Kao is an Assistant Professor in the Department of Neurology at the University of California, San Francisco.  Her post-doctoral training includes fellowships with Dr. Bruce Miller on the genotype-phenotype connection in neurodegeneration and Dr. Cynthia Kenyon on the molecular genetics of diseases of aging.  Her laboratory focuses on the basic mechanisms of neurodegenerative disorders such as Alzheimer's Disease and frontotemporal lobar degeneration. Her recent work has shed light on how stress, inflammation and cell death mechanisms contribute to impaired proteostasis and neuron loss.