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Link between Alzheimer’s disease and epilepsy explored

Neuroscience researchers have found common genes involved in dysregulation in brain tissue samples from people with Alzheimer’s disease (AD) and temporal lobe epilepsy (TLE).

People living with Alzheimer’s disease (AD) have an increased risk of developing seizures, in fact a 10-fold increased risk that increases in people with early or familial AD. Conversely, people with epilepsy have a high risk of developing dementia*, suggesting a bidirectional relationship between the two neurological diseases.

Researchers from the Kwan group in the Department of Neuroscience have discovered two modules associated with synaptic signaling driven by the SCN3B and EPHA4 genes and and two modules associated with neurogenesis driven by the GABRB3 and SCN2A be deregulated in brain tissue samples from individuals with Alzheimer’s disease (AD), temporal lobe epilepsy (TLE), indicating similar rewiring that may be involved in molecular mechanisms.

Electrical abnormalities (epileptiform activity) occur in temporal brain regions in people with AD. Temporal lobe epilepsy is a common subtype of epilepsy that results in focal seizures and has pathophysiology similar to AD (eg, tau pathology, amyloid deposition, and hippocampal sclerosis). However, the underlying pathophysiology and causal relationships between the two diseases are poorly understood.

Weighted gene coexpression network analysis (WGCNA) and statistical network preservation methods were applied to gene networks for temporal lobe epilepsy, AD and controls (see diagram above).

Dr Alison Anderson, lead author of the study, said: ‘What we found are specific defects in the molecular mechanisms that are shared between the two neurological diseases. This discovery is particularly important because it may uncover the cause of the development of epilepsy in AD and open new doors to more targeted treatment options for patients.

Anna Harutyunyan, PhD student (Jones Group), said: “As first author, along with senior author Dr Alison Anderson, we are among the very few women (probably

Reference

Harutyunyan, A, Jones, NC, Kwan, P, Anderson, A. Network preservation analysis reveals dysregulated synaptic modules and shared regulatory centers between Alzheimer’s disease and temporal lobe epilepsy. Frontiers in genetics. 2022; 13, https://doi.org/10.3389/fgene.2022.821343.

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*Central Clinical School’s Consumer and Researcher Engagement Committee (CARE) is hosting a Dementia Webinar on May 18 at 5:30 p.m. – see details and register