A significant role of comorbid epilepsy in the pathophysiology of Alzheimer’s disease

Akira Kuzuya, Masakazu Miyamoto, Sakiho Ueda

Department of Neurology, Kyoto University Graduate School of Medicine

It has been well known that some patients with Alzheimer’s disease （AD） experienced epileptic seizures such as complex partial seizures, generalized convulsions and myoclonic seizures, particularly in the advanced stages.　On the other hand, it has been cleared that pathological changes occurred in AD brains begin to precede the onset of cognitive impairment by more than 20 years, according to developments in the diagnostic techniques using biomarkers.　While preemptive medicine targeting the early stages of AD including the preclinical phase is recently highlighted, new evidence is accumulating that subtle complex partial seizures or subclinical seizures observed in the early stages of AD are much more common than expected.　In addition, recent clinicopathological reports using brain specimens resected from patients with refractory temporal lobe epilepsy （TLE） for epilepsy surgery have shown that deposition of amyloid-β protein and hyperphosphorylation of tau protein, similar to those of AD brains, are found in refractory TLE brains, indicating a potential pathological link between AD and epilepsy.　Based on the findings obtained from clinical studies towards both AD and epilepsy, we propose a vicious cycle model via the bidirectional relationship between the two diseases, under which epileptic condition can promote cognitive dysfunction and neurodegenerative processes in AD.　In a near future, progress in bidirectional translational research between clinical and basic science, focusing on the comorbidity between AD and epilepsy, could lead to a new and promising therapeutic strategy for AD targeting neuronal network hyperexcitability.　We will outline this theme as AD researchers, presenting our case reports in addition to previous reports of basic and clinical studies.

Address correspondence to Akira Kuzuya MD, PhD, Department of Neurology, Kyoto University Graduate School of Medicine （54 Shogoin-Kawaharacho, Sakyoku, Kyoto 606-8507, Japan）