Link between Alzheimer’s Disease and epilepsy explored – Medicine, Nursing and Health Sciences – Monash University

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By Loretta Piccenna 08 April 2022

Neuroscience researchers have foundgenes in common involved in dysregulation in brain tissue samples of people with Alzheimers Disease (AD) and temporal lobe epilepsy (TLE).

People living with Alzheimers Disease (AD) have an increased risk of developing seizures, in fact a 10-fold risk which grows higher in people with early onset 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 within the Department of Neuroscience have found two synaptic signalling-associated modules driven by the SCN3B and EPHA4 genes and and two neurogenesis-associated modules driven by the GABRB3 and SCN2A to be dysregulated in brain tissue samples of people with Alzheimers Disease (AD), temporal lobe epilepsy (TLE), indicating similar rewiring that may be involved in the molecular mechanisms.

Electrical abnormalities (epileptiform activity) occur in the temporal brain regions in people with AD. Temporal lobe epilepsy is a common subtype of epilepsy that results in focal seizures and has a similar pathophysiology with AD (e.g. 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 network preservation statistics methods were applied to gene networks for temporal lobe epilepsy, AD and controls (see schema above).

Dr Alison Anderson, senior author of the study said, What we found were specific defects in molecular mechanisms that are shared between the two neurological diseases. This finding is particularly important as it may uncover the cause of how epilepsy develops in AD and open up new doorways for more targeted treatment options for patients.

Anna Harutyunyan, a PhD student (Jones Group), said, As first author, together with seniorauthor Dr Alison Anderson, we are among the very few women (probably <10%) that have contributed to the journals topic where our study was published - Advanced computational strategies to tackle human complex diseases. The team were also the only Australian group who have published their research in this topic.

Reference

Harutyunyan, A, Jones, N.C., Kwan, P, Anderson, A. Network Preservation Analysis Reveals Dysregulated Synaptic Modules and Regulatory Hubs Shared Between Alzheimers 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 (CARE) Committee is hosting a webinar on dementia on 18 May at 5.30 pm - see details and register

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Link between Alzheimer's Disease and epilepsy explored - Medicine, Nursing and Health Sciences - Monash University