The Impact of Head Impacts on Neurodegeneration

Le résumé fourni par la source

Single and repetitive head impacts are recognized risk factors for neurodegenerative diseases. This thesis aimed to identify pathophysiological pathways, clinical characteristics, and potential biomarkers associated with neurodegeneration following such impacts. In Part I, we investigated the effects of traumatic brain injury (TBI) on Alzheimer’s disease (AD). Our findings showed no distinct impact of TBI on the clinical presentation or cognitive decline in AD. However, we identified that TBI occurring before the age of 25 was associated with an earlier onset of AD. In Part II, we shifted focus to neurodegeneration linked to repetitive head impact (RHI) exposure. We examined the neuropathology and clinical presentation of a former professional soccer player with dementia, identifying chronic traumatic encephalopathy (CTE) pathology. Our findings highlighted that CTE-related neurodegeneration can clinically resemble AD. Parts III and IV explored in vivo clinical and pathophysiological characteristics by assessing cerebrospinal fluid (CSF), blood biomarkers, and neuroimaging findings in individuals with prior RHI exposure. We identified multiple factors potentially contributing to neuropsychiatric symptoms in these individuals, including neuroinflammatory, neurodegenerative, and catecholaminergic processes. Additionally, we observed that RHI exposure was associated with long-term decreased concentrations in CSF biomarkers reflecting norepinephrine and dopamine pathways. Furthermore, plasma biomarkers of AD pathology correlated with cognitive performance in RHI-exposed individuals. In conclusion, our findings suggest that TBI has a limited impact on the clinical and pathophysiological characteristics of AD. RHI exposure may be associated with a range of pathophysiological processes beyond CTE-specific p-tau pathology, including neuroinflammation, neuronal loss, and catecholaminergic dysregulation, some of which may contribute to cognitive and neuropsychiatric symptoms. These altered biological pathways offer potential targets for biomarker development in the context of CTE and emphasize the urgent need for disease-specific biomarkers.

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