Reducing Tau as a Therapeutic Strategy for Improving Cognitive Dysfunction in Parkinson’s Disease

Posted January 8, 2021

Laura A. Volpicelli-Daley, Ph.D., University of Alabama Birmingham

Dr. Laura A. Volpicelli-Daley Dr. Laura A. Volpicelli-Daley

One of the most burdensome effects of PD is cognitive change. Treatments for cognitive effects provide little relief for most patients and do not prevent progressive deterioration. Dr. Laura A. Volpicelli-Daley received a DOD award to examine whether the protein tau is implicated in PD, as it is in other neurological conditions.

Dr. Payami Figure Reducing tau inhibits the formation of seeded α-synuclein formation in the amygdala and cortex

Knowing that the genes for tau and alpha-synuclein are consistently associated as risk factors for PD, she asked whether tau and alpha-synuclein interact to cause cognitive changes in PD and whether the absence of tau would prevent neuronal dysfunction and behavioral defects in cognition and mood disorders. Her hypothesis was that the tau protein causes neuronal dysfunction before development of alpha-synuclein aggregates, and initiates the cognitive dysfunction seen in PD. Working with Dr. Erik Roberson, an expert in tau at University of Alabama Birmingham, Dr. Volpicelli-Daley, used a novel mouse model with reduced or abolished tau levels. Alpha-synuclein fibrils were injected into neurons in the striatum to induce formation of alpha-synuclein inclusions in brain regions important for cognitive function.

Findings from Dr. Volpicelli-Daley’s study and additional published research suggests that reducing tau prevents the formation of fibril-induced alpha-synuclein inclusions and improves behavioral tests of cognition.

“I received a Career Progression Award from the DOD in 2015 that helped launch my career as a tenure-track assistant professor at the University of Alabama Birmingham. NIH funding and R01 grants are difficult to obtain for an early-career researcher without prior awards that substantiate their contributions to science.”

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