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.

Congratulations to Mr Hattapark Dejakaisaya on his PhD completion

Congratulations to Mr Hattapark Dejakaisaya on his PhD completion, on 3 Feb 2022! 

Hattapark's thesis is titled "The Role of Glutamate in the Pathogenesis of Acquired Epilepsy in Alzheimer's Disease". He was supervised by Professor Patrick Kwan  and Associate Professor Nigel Jones, both in Department of Neuroscience at CCS.

He writes, "Alzheimer’s disease (AD) patients have up to 10-fold higher risk of developing epilepsy compared to healthy controls. However, the mechanism that links AD pathologies to epileptic seizures is not elucidated. We do know that disruption to glutamate-glutamine cycle in the brain caused by AD has the potential to enhance this risk. 

Study highlights gap in ageing brain research

L-R: Dr Mujun Sun (first author) and A/Prof

Sandy Shultz (last author)

by Anne Crawford

Neurological conditions such as traumatic brain injury, stroke, Parkinson's disease, epilepsy, multiple sclerosis and Alzheimer's disease are leading causes of morbidity and mortality affecting millions of people worldwide. Yet the majority of clinical trials testing drugs for these common conditions have failed.

The Department of Neuroscience’s Associate Professor Sandy Shultz is among a growing number of scientists asking whether the failure to translate findings of preclinical studies to the clinic is because many patients with these conditions are middle-aged or older, yet most preclinical studies test only young adult animals.

Walking the walk: using gait to gauge dementia

by Anne Crawford

Monash University Central and Peninsula Clinical School researchers have shown that a person’s gait can predict whether they are headed for dementias such as Alzheimer’s disease, and which specific brain functions are involved in this cognitive decline.

Associate Professor Michele Callisaya and Professor Velandai Srikanth, supervising first author PhD student Ms Oshadi Jayakody from the University of Tasmania, investigated whether variability from one step to the next during walking, and gait speed, were related to cognitive decline over time. Their study was published in the Journal of Alzheimer’s Disease.

Media mention: Alzheimer's trial using TMS

A/Prof Kate Hoy

Articles on A/Prof Kate Hoy's clinical trial treating cognitive symptoms of mild to moderate Alzheimer's with TMS (Transcranial Magnetic Stimulation)

16 Mar 2017 Channel 9 https://www.9now.com.au/today/2017/clip-cj0bte7av00bu0gloc3ow3nq4

15 Mar 2017 SMH, Age http://www.smh.com.au/technology/sci-tech/brain-stimulation-for-alzheimers-disease-patients-shows-promise-20170313-guwz2p.html

14 Mar 2017 Herald Sun  http://www.heraldsun.com.au/news/victoria/magnets-to-manipulate-brain-activity-latest-therapy-to-improve-early-symptoms-of-alzheimers-disease/news-story/75530cd8939c742371c2c9d2cf447dfe

Congratulations to Sara Mokhtar on her PhD completion!

Sara Mokhtar won the CCS 3MT thesis heat
in 2014. See video

Congratulations to Sara Mokhtar, who has fulfilled the requirements for the degree of Doctor of Philosophy. Her thesis is titled: "The amyloid-beta-dependent phosphorylation of CRMP-2 and its contribution in Alzheimer's disease". Sara was supervised by Dr Steven Petratos (Medicine CCS) and Professor Richard Boyd (ARMI).

Alzheimer’s disease (AD) is the most common form of dementia in the elderly. AD causes loss of memory, cognition, language and emotional stability and has currently no known cure. The aim of Sara's project was to find a novel target to stop the progression of the disease in order protect our aged population. It is well known that AD is caused by the accumulation of a normal protein in the brain called beta amyloid (Aβ).

Unlocking the brain with new stimulation technologies

Associate Professor Kate Hoy

Brain connectivity and neuroplasticity are increasingly investigated and becoming better understood, and the insights are being employed with new technologies for treatment of cognitive disorders and brain injuries.

In this article, Elouise Brennan interviews A/Prof Kate Hoy of the Monash Alfred Psychiatry research centre on how the techniques of transcranial direct current stimulation and transcranial magnetic stimulation are being used for schizophrenia, Alzheimer's and depression. Link to full story.

Video: Elsdon Storey on neurodegenerative diseases research

Professor Elsdon Storey is Director of the Van Cleef/Roet Centre for Nervous Diseases, in the Department of Medicine at Central Clinical School, and Head of Neurology at the Alfred Hospital, at the Alfred Medical Research and Education Precinct. The Centre's research focuses on neurodegenerative disorders affecting coordination, movement, balance and cognitive function particularly using animal models. Diseases such as Parkinson's, Alzheimer's 5:43, and ataxias are investigated. Youtube link: https://www.youtube.com/watch?v=aA6Srh_DSz8

Investigating Alzheimer's disease

PhD student Judy Allen-Graham completed her thesis in 2012, titled ‘Inhibition of APP and APLP2 using siRNA to investigate protein function and Alzheimer's disease’, on functional redundancy between the Alzheimer’s protein APP and its homologue APLP2. APP, the amyloid precursor protein of Alzheimer’s disease, and its homologue APLP2 are found in a segmental distribution on the surface of neurites in cortical neurons in primary culture.