Melanie Alpaugh

, Dr. Francesca Cicchetti, Laval University, Canada

Interrogating blood samples from Huntington’s disease patients to better understand cognitive impairments

Cognitive decline is a major clinical symptom of Huntington’s disease (HD), which often appears early in disease and inevitably impacts the patient’s quality of life. However, there are currently no reliable tools to predict which individuals are likely to develop cognitive deficits. Identification of factors in the blood that can be used to track such symptoms would have important implications for clinical trials as well as symptom management. In this study, we propose to investigate various elements of the blood to determine if they may be able to serve as a predictor of vulnerability to cognitive deficits. First, we will evaluate tau, a protein present in brain cells that helps maintain their internal skeleton. In several brain disorders, tau aggregates in clumps and impairs neuronal function. Tau has a well-described role in Alzheimer’s disease, however, other disorders such has Parkinson’s disease and HD have also been described to have tau pathology. The commonality of tau pathology to multiple nervous system disorders presenting with cognitive decline suggests that the presence of tau may contribute to this aspect of disease. Further evidence of this relationship in HD comes from studies demonstrating that different versions of the tau gene correlate with cognitive decline and its severity in patients. Aside from tau, we plan to isolate extracellular vesicles, small structures that carry information/messages between cells. Vesicles are interesting as they move readily between the brain and the blood, meaning that we can use vesicles found in the blood as a window into the health of brain cells. By exploring one specific and one more general marker of neuronal health, we aim to both identify novel indicators and to increase our understanding of which neuronal changes relate to the development of cognitive impairments.