Epilepsy and Alzheimer's Disease: Potential mechanisms for an association

Alzheimer's Disease (AD) and epilepsy are common neurological diseases. The prevalence of epilepsy in AD patients is higher than in healthy subjects, but identifying the reasons for this association, the characteristics of seizures in AD, and the implications for prognosis and treatment is challenging. The present review provides first of all an overview of the main clinical aspects of AD and epilepsy, of their reciprocal relationship, and of the challenges that identifying seizures in AD patients presents. Limitations of clinical studies addressing this topic are discussed, including their mostly prospective nature and possible selection biases. A comprehensive, mechanistic discussion on the factors that are most likely to underlie the increased risk for seizures in AD follows. These include, for instance, GABAergic and glutamatergic alterations, Aβ and Tau protein, the role of the noradrenergic nucleus Locus Coeruleus, and neuroinflammation. Finally, evidence concerning the role that epilepsy may have in exacerbating or initiating AD is reviewed. A mechanistic insight on the relationship between epilepsy and AD might have relevant implications for improving the treatment of AD patients, as well as in elucidating pathophysiological mechanisms.