Uncovering the mechanisms linking epilepsy and Alzheimer’s Disease with computational genetics

Study overview

by Dr Loretta Piccenna, Department of Neuroscience

People living with Alzheimer’s 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 Alzheimer’s 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

Anna Harutyunyan, a PhD student (Jones Group), said, “As first author, together with senior author Dr Alison Anderson, we are among the very few women (probably <10%) that have contributed to the journal’s 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 Alzheimer’s Disease and Temporal Lobe Epilepsy. Frontiers in Genetics. 2022; 13, https://doi.org/10.3389/fgene.2022.821343

 

*Your chance to find out more of the dementia research at Central Clinical School: The Consumer and Researcher Engagement (CARE) Committee is hosting a webinar on dementia on 18 May at 5.30 pm - see details and register.