Cruces, R. R.; Lam, J.; Arafat, T.; Royer, J.; Chen, J.; Sahlas, E.; Dascal, A.; Pana, R.; Hopewell, R.; Hsiao, C. H.-H.; Massarweh, G.; Soucy, J.-P.; Villeneuve, S.; Caciagli, L.; Koepp, M. J.; Bernasconi, A.; Bernasconi, N.; Bernhardt, B.

Temporal lobe epilepsy (TLE), the most common pharmaco-resistant epilepsy in adults, has been linked to structural brain changes extending beyond the mesiotemporal areas. While not traditionally viewed as a neurodegenerative disorder, recent ex-vivo studies have shown elevated levels of misfolded tau protein in TLE. This study investigated tau deposition in TLE patients using the in-vivo PET tracer [18F]MK-6240. 18 TLE patients and 20 healthy controls underwent PET imaging, with data analyzed to assess tau uptake and its relationship with brain connectivity, clinical variables, and cognitive function. Compared to controls, TLE patients exhibited markedly increased [18F]MK-6240 uptake in bilateral superior and medial temporal regions and the parietal cortex, with tau accumulation following regional functional and structural connectivity, disease duration, and cognitive impairment. These findings suggest that tau accumulation may contribute to the progression of TLE and cognitive decline, supporting a potential role of tau in epilepsy-related neurodegeneration.