Traumatic Brain Injury and Parkinsonism
Epidemiologic studies have reported a strong association of traumatic brain injury with an increased risk of developing parkinsonism. Animal studies have described a putative link between Parkinson's disease and prior clinical history of traumatic brain injury, an observation that was confirmed in a population-based case-control study on a large cohort of patients with a well-characterized Parkinson's disease phenotype.
Deposits of aggregated alpha-synuclein have been found in neurons and axons following a single brain insult in humans as well as in animal models of brain injury. Furthermore, alpha-synuclein is elevated in the cerebrospinal fluid of patients with brain injuries and can be used as a biomarker for diagnosis and prognosis.
Despite these observations the mechanistic link between brain injury and parkinsonism remains poorly understood. Dr. McLean's lab is interested in investigating the mechanistic link between brain injury and alpha-synuclein aggregation.
We hypothesize that a traumatic brain injury can damage neural tissue and induce the release of cellular breakdown products from damaged cells in the surrounding area. The cellular breakdown products can then act on neighboring healthy cells and promote intracellular alpha-synuclein aggregation.
We have shown that adenosine triphosphate (ATP) released from damaged cells can induce aggregation of alpha-synuclein in vitro and we propose that similar mechanisms may occur following brain injury. Current studies in the Neurobiology of Parkinson's Disease Lab are investigating whether extracellular ATP increases following a traumatic brain injury and facilitates alpha-synuclein aggregation.