July 19, 2018

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-? (A?) 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 Alzheimer’s disease as a consequence of neurodegeneration, however, recent studies indicated that seizures may contribute to the emergence of Alzheimer’s disease symptoms in early stages of the disease, mainly in familial Alzheimer’s disease. 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 early-onset familial Alzheimer’s disease, focusing on possible overlapping pathological mechanisms.

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