+44 7480725689 Delia M. Talos
University of Pennsylvania, USA
ScientificTracks Abstracts: Neurosci
Statement of the Problem: Cognitive impairment is a frequent epilepsy comorbidity. On the other hand, seizure risk in neurodegenerative cognitive disorders such as Alzheimer�s disease (AD) is higher than in the general population, suggesting a potential bidirectional relationship between epilepsy and dementia. Indeed, epidemiological studies reveal that people with epilepsy and individuals with AD share common risk factors, yet the underlying mechanisms are poorly understood. We hypothesized that the cognitive impairment in drug-resistant epilepsy could be due to perturbations of amyloid and tau signalling pathways, similar to those observed in Alzheimer�s disease, and that in AD, seizures could accelerate disease progression. Methodology & Theoretical Orientation: To elucidate our proposed bidirectional relationship between AD and seizures, we studied temporal lobe epilepsy (TLE) surgery cases and post-mortem AD human brain samples from patients with and without known seizure history, using western blot and immunohistochemical analysis. Findings: First, we found increases in beta-amyloid (1-42) peptide, the main component of amyloid plaques, and pathologic phosphorylation of two distinct tau species in tissue samples from therapy-resistant TLE cases. Further analysis revealed a strong association between amyloid and taupathologies and cognitive deficits, and identified aging as a risk factor for the development of AD-like pathological changes in TLE. In addition, we found that AD patients with a history of seizures had increased amyloid and tau pathology, and overall more pronounced brain atrophy, when compared to cases without known seizure history. Conclusion & Significance: These data demonstrate an important link between chronic hyper excitability, cognitive decline and progressive AD-like pathology. Our study also provides a rationale for the use of inhibitory agents currently tested in AD to treat epilepsy patients with cognitive deficits, and highlights the importance of early epilepsy diagnosis and treatment in AD patients.
Dr. Talos is an Assistant Professor of Neurology at the University of Pennsylvania, Perelman School of Medicine, with an active research program in epilepsy. Her research focuses on mechanisms of epilepsy and its interaction with other disorders such as autism and dementia, with emphasis on age-specific mechanisms and therapeutics. Her laboratory uses several mouse models and in vitro brain slices to test the efficacy of new therapies to suppress the occurrence of seizures and the development of chronic epilepsy. In parallel, the laboratory uses human tissue to conduct basic cellular and molecular studies to reveal novel therapeutic targets and to relate findings in experimental models to the human pathology.
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