Epileptic seizures in autosomal dominant forms of Alzheimer's disease

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disorder and represents the most common form of dementia in the elderly. Mutations in genes encoding presenilin 1 (PSEN1), presenilin 2 (PSEN2) and amyloid precursor protein (APP) are responsible for early-onset familial AD (EOFAD). Several pieces of evidence report that patients with rare autosomal dominant forms of AD carry a significant risk to develop seizures. However, the molecular mechanisms linking epilepsy and AD are needed to be clarified: the pathophysiology of seizures in AD may be related to an increased production of amyloid-β (Aβ) peptide or structural alterations in neurons probably due to cerebrovascular changes, neurotransmitter or cytoskeletal dysfunctions. Seizures have traditionally been related to neuronal loss in the late stages of AD as a consequence of neurodegeneration, however, recent studies indicated that seizures may contribute to the emergence of AD symptoms in early stages of the disease, mainly in familial AD. So, a better understanding of possible common neural mechanisms might help to improve the clinical management of both conditions. This review aims to give a comprehensive overview and to analyze the association between epilepsy and EOFAD, focusing on possible overlapping pathological mechanisms.