Tau Protein in Drug-Resistant Epilepsy and Cognitive Decline

Cognitive impairment is common in individuals with epilepsy and can be progressive for some. The multifactorial causes of cognitive impairment depend on the underlying aetiology as well as the severity of epilepsy. Abnormal neuronal activity is observed in both epilepsy and Alzheimer’s disease; epilepsy may increase the risk of neurodegeneration and vice versa. Neuropathology of surgically resected tissues from patients with drug-resistant epilepsy reports age-accelerated pTau accumulation and variable levels of β-amyloid that have been compared with known tauopathies, including chronic traumatic encephalopathy. Epilepsy-specific patterns of pTau may reflect specific cellular drivers and pathways, including the mammalian target of rapamycin (mTOR), oxidative stress and neuroinflammatory pathways, providing novel therapeutic targets. This chapter addresses the existing evidence for the role of tau protein in epilepsy primarily based on neuropathological studies, its contribution to cognitive decline and future research directions.