Seizures in Alzheimer's disease

Area of Science:

• Neuroscience
• Neurology
• Gerontology

Background:

• Alzheimer's disease (AD) is associated with an increased risk of late-onset seizures and neuronal network dysfunction.
• Both sporadic and familial forms of AD exhibit a higher co-occurrence of seizures, particularly in cases with specific genetic mutations (PSEN1, PSEN2, APP) or APP duplication.
• Emerging evidence indicates that nonconvulsive network abnormalities, including electroencephalographic abnormalities, are more prevalent in AD patients than previously recognized.

Purpose of the Study:

• To review the relationship between Alzheimer's disease and seizures, focusing on underlying mechanisms and potential therapeutic interventions.
• To explore the role of amyloid-beta (Aβ) and amyloid precursor protein (APP) in cortical network hyperexcitability and epileptiform activity in AD.
• To summarize findings from AD mouse models and human studies regarding seizure activity and cognitive deficits.

Main Methods:

• Review of existing literature on Alzheimer's disease, seizures, and electroencephalography (EEG) studies.
• Analysis of studies involving AD mouse models to investigate seizure activity and APP/Aβ roles.
• Examination of clinical studies on antiepileptic drug (AED) efficacy in AD patients and models.

Main Results:

• Amyloid-beta (Aβ) and full-length amyloid precursor protein (APP) are implicated as key factors linking AD and seizures, potentially driving cortical hyperexcitability.
• Nonconvulsive epileptiform activity, characterized by frequent, short-duration abnormalities, may contribute to AD-related cognitive impairments, such as memory deficits.
• Studies in AD mouse models and human patients suggest that antiepileptic drugs may offer a therapeutic strategy to mitigate cognitive decline.

Conclusions:

• A mechanistic link exists between epileptiform activity and Alzheimer's disease, highlighting neuronal hyperexcitability as a critical area of research.
• Understanding the interplay between seizures and AD progression is crucial for developing effective treatment strategies.
• Targeting epileptiform activity with antiepileptic drugs presents a promising avenue for improving cognitive outcomes in Alzheimer's disease patients.