Todd Cohen, PhD

Novel Post-translational Mechanisms that Mediate Neurodegeneration in Aging and Alzheimer’s Disease

Dr. Cohen’s lab is exploring new molecular approaches to address how brain pathology develops in aged and Alzheimer’s disease subjects. The lab’s main focus is to determine what causes tau proteins to accumulate in the brain.

It is generally well accepted that the accumulation of tau proteins in the brain triggers, in part, the cognitive decline seen in Alzheimer’s disease and other age-related neurodegenerative diseases. If Dr. Cohen and his group can define the factors that promote tau aggregation, they could potentially devise future therapies that will prevent it from happening.

Dr. Cohen’s team is studying a new post-translational signaling modification on tau known as acetylation, which may promote tau aggregation. (Acetylation is a reaction that introduces an acetyl functional group onto a cellular protein.) Dr. Cohen and his group detected high levels of acetylated tau tangles in all human Alzheimer’s disease patients they analyzed, but never detected acetylated tau in any non-diseased individuals.

Tau acetylation is still a poorly understood process, and Dr. Cohen’s lab is the first to genetically elevate tau acetylation by removing HDAC6, one of the major tau deacetylases. He and his team anticipate that HDAC6 depletion will increase tau acetylation in the brain and lead to accelerated neurodegeneration. Their results could provide a new framework to model human Alzheimer’s disease and shift their focus towards other potentially druggable enzymes as unanticipated targets in the treatment of Alzheimer’s disease.