About us
About us

The ForeFront research program brings together a unique research group of internationally recognised leaders in clinical, pathological and biological research on neurodegenerative dementias (including frontotemporal dementias, Lewy body dementias, early onset dementia and Alzheimer’s disease), motor neuron disease, neurodegenerative movement disorders (including Parkinson’s disease, multisystem atrophy and progressive supranuclear palsy), along with healthy brain ageing.

With over 300 researchers and professional research staff collaborating across cutting-edge clinical and laboratory-based areas, ForeFront aims to develop early detection and treatment for these neurodegenerative diseases.

Our Mission

Our ForeFront research groups work together to help reduce impact on patients, family and society by improving the services offered to those affected, enhancing support for carers and offering new hope through clinical trials and the development of novel treatments based on new knowledge about these diseases.

Our long-term goal is to improve and expedite diagnosis and to better understand how neurodegenerative processes work so that we can treat and potentially halt these debilitating diseases.

Our Research

To achieve our goals, ForeFront research is organised into two main areas:

  • Clinical research - Diagnosis, care and treatments of neurodegenerative diseases
  • Laboratory-based research - Biology of neurodegenerative diseases, including identification and development of clinical biomarkers and novel treatments

Our research is not possible without the involvement of many people that are affected or impacted by ageing and neurodegenerative diseases. If you wish to be involved, please contact us.

Brain Ageing

Ageing is known to affect many different systems in your body, with the word itself implying a change in your biology. How your brain ages is now known to be an important determinant of whether you will need more or less assistance during life as you get older.

The biggest risk factor for neurodegenerative diseases is ageing itself, something none of us can do anything about. However, maintaining a healthy life style by eating well and avoiding obesity, diabetes, hypertension and tobacco smoking, keeping physically, socially and intellectually active, and preventing and treating hearing loss, all keep your brain in the best condition you can manage.

We know that not everyone who gets older gets a neurodegenerative disease, so other factors are also important. We also know that not everyone who lives healthily is immune to neurodegeneration, or that older people with less than optimal health will all have neurodegeneration.

Understanding more about how people can maintain their brain health into older age and prevent neurodegenerative diseases is an important part of our research.

Learn more about our healthy ageing program.

Neurodegenerative dementias

It is estimated that just under half a million Australians are currently living with dementia. Neurodegenerative dementias are heterogeneous brain disorders caused by the abnormal aggregation of proteins in the brain. These changes lead to the progressive death of brain cells (atrophy) and the emergence of different clinical syndromes (e.g., Alzheimer’s disease, Lewy body dementias, frontotemporal dementias, etc.). Accurate diagnosis and prognosis in dementia is challenging and despite years of continuing research, the most accurate diagnoses are monitoring of brain regions undergoing atrophy during life.

Alzheimer’s disease, Lewy body dementias and frontotemporal dementias have shown a remarkable rise in prevalence in Australia. Alzheimer’s disease alone already affects over 300,000 Australians, with numbers expected to grow to 730,000 by 2050. In fact, in females, dementia has displaced heart disease as the leading cause of death. At present, there are no cures or disease-modifying therapies for any of these diseases.

A key problem to treating these diseases is understanding and identifying the heterogeneity of the underlying protein changes. Determining causes and biomarkers for these changes is a focus of our laboratory-based research.



The ForeFront dementia research teams focus on the following 3 areas:

Alzheimer’s disease is the most common form of dementia accounting for approximately 70% of all dementia cases. Alzheimer’s disease is clinically characterised by memory loss, confusion and changes in mood and personality. Rare, genetic mutations cause Alzheimer’s disease in a very small percentage of cases (<0.5% cases), however the cause of the remaining 99% of clinical cases is still unknown.

Multiple genetic and lifestyle risk factors have been shown to increase the risk of clinical Alzheimer’s disease, however none of these have yet been shown to independently cause the disease. This may be due to the brain changes beginning 20 years or more before the cognitive symptoms appear, so the proximate causal factors have not been identified.

The early brain changes are now measured using neuroimaging techniques and protein differences in the cerebrospinal fluid that surrounds the brain, and also in the blood.

The characteristic changes in the brain of people with Alzheimer’s disease include the development of amyloid plaques, neurofibrillary tangles and neuron death in distinct brain regions that are particularly vulnerable to the disease. Our research is identifying the protein changes that develop over time for treatment targets.

While clinical trials for Alzheimer’s disease are ongoing, the lack of any real therapeutic advances is perceived to be due to the trial of treatments at the end stages of the disease, rather than at the time the early changes are observed. We are part of national and international research studies trying to treat the disease at earlier stages.




Dementia with Lewy bodies and Parkinson’s disease dementia are jointly called Lewy body dementias and are the second most common form of dementia other than Alzheimer’s disease in older adults. Clinical features include:

  • Progressive cognitive decline
  • Visual hallucinations
  • Fluctuations in alertness and attention
  • Sleep disorders
  • Autonomic dysfunction
  • Delusions
  • Depression
  • Motor signs of Parkinson's disease (such as ridigity, difficulty walking, slowness of movement and postural instability).

Despite being the second most common neurodegenerative dementia in the elderly, research into this disease is not as well advanced as for Alzheimer’s disease, and it is commonly clinically misdiagnosed as Alzheimer’s disease because of overlap in clinical presentations.

Accurrate diagnosis is essential for Lewy body dementias, as it has been known for some time that the disease can get worse on some drugs used for the symptomatic relief in Alzheimer’s disease. Our research has been determining the best methods for accurate diagnosis and the techniques are being used in new clinical trials.

The underlying common brain change is called a Lewy body, a cellular inclusion that builds up or aggregates a common protein found in nerve cells called alpha-synuclein. Again, these brain changes occur well before the clinical symptoms of dementia occur, and our research is determining how these inclusion impact on brain cells.




Frontotemporal dementias (FTD) are a common cause of younger-onset dementia affecting ~15 per 100,000 people between the ages of 45-64 years. Clinically FTD is an underappreciated cause of younger-onset dementia and is commonly misdiagnosed as Alzheimer’s disease because of overlap in clinical presentations, even though the areas of the brain affected and the types of underlying cellular pathologies differ from those of Alzheimer’s disease. There is a strong genetic basis to FTD with a number of genes now identified. Our research focusses on identifying new genes and using genetic information and genetic material to assist with diagnosis.

People with FTD show either early changes in behaviour and personality, or difficulties with language. Often these clinical problems lead to difficulties in interactions in social situations. For example, patients with behaviour and personality changes can become less empathetic, show a loss of motivation and can act inappropriately. These behavioural changes can be very distressing for family members and carers, and can lead to people becoming socially isolated. Our clinical research aims to determine how to diagnose and treat these difficulties.

The cellular changes observed in the brains of people with FTD are diverse with cellular inclusions made of one of three proteins (tau, TDP-43 or FUS). At present the type of inclusion can only be determined postmortem and cannot be predicted by the clinical features. We are working hard to understand more about these protein changes and how they change brain cell behaviour to cause disease. Another major objective is to develop blood biomarkers to objectively distinguish FTD patients from other dementias and those without dementia.




Motor Neuron Disease

The motor neurons are nerves that extend from the brain to the spinal cord and muscles and provide the stimulus through which we move, breathe, eat and drink.

Motor neuron disease (also known as amyotrophic lateral sclerosis or ALS) is a rapidly progressive disease that causes the death of motor neurons leading to paralysis and death. Motor neuron disease is a devastating illness with appalling prognosis. It occurs sporadically in ~90% of patients and the average survival is 2.5 years from symptom onset. There is currently no cure for motor neuron disease, with available therapies only able to prolong life expectancy by 3 months.

Our research aims to model and track stages of disease evolution in motor neuron disease using cutting edge multi-modal neuroimaging techniques in combination with artificial intelligence-based modelling. We have identified selective patterns of change in structural pathways of the brain that are associated with clinical symptoms and phenotypes. We are currently working on translating these findings into clinical models for predicting the disease trajectory using deep learning neural networks. This research will allow diagnosis as early as possible in order to maximise new clinical treatments in our clinical trials.

The only proven causes of motor neuron disease are gene mutations that lead to motor neuron death. Identification of the genes that cause or predispose someone to motor neuron disease will lead to the unravelling of the underlying molecular mechanisms.

The cellular changes in motor neuron disease are a build up of the protein known as TDP-43. Many of our cellular research projects are aimed at understanding how this affects cells in order to identify potential new cellular treatment targets (Read more about our laboratory-based research on MND here).




Neurodegenerative movement disorders

The most common neurodegenerative momement disorder is Parkinson’s disease, but a number of other diseases can mimic Parkinson’s disease. These include multiple system atrophy and progressive supranuclear palsy. In the last two decades we have learnt that patients who develop a movement disorder often have REM sleep behaviour disorder before they get their movement disorder. REM sleep behaviour disorder is defined as the loss of the normal paralysis during sleep (causing affected people to ‘act out their dreams’). This discovery offers a unique window for understanding the natural progression of these disorders but also the potential for trialling neuroprotective treatments prior to significant neurodegeneration.



The ForeFront researchers are studying a range of movement disorders, including:

Parkinson’s disease has a wide variety of clinical symptoms, including classic motor features (i.e. tremor, rigidity, bradykinesia, and postural instability) and non-motor symptoms such as cognitive impairment, sleep disturbances, depression, and hallucinations. Different people can vary quite markedly in their symptoms, however the reasons for this have not been firmly established. We hope to have a better understanding of the causes of the problems faced by people living with Parkinson’s disease through the utilisation of a range of techniques such as neuroimaging (brain scanning) and neurophysiology (e.g. recording brain waves).

Like motor neuron disease, Parkinson’s disease occurs sporadically in ~90% of patients, although a number of different genes cause of Parkinson’s disease. Identification of the genes that cause or predispose people to Parkinson’s disease will also lead to the unravelling of the underlying molecular mechanisms.

The cellular changes in Parkinson’s disease are similar to that seen in Lewy body dementias. Many of our cellular research projects are aimed at understanding how this affects cells in order to identify potential new cellular treatment targets.

There are no approved disease modifying therapies for Parkinson’s disease, so we are also currently conducting a series of disease modifying drug trials in patients who have been diagnosed with Parkinson’s disease.




Multiple system atrophy is as common as motor neuron disease. Is it caused by the deposition of alpha-synuclein in brain cells, although the type of cells involved differs from those depositing the protein in the brains of people with Parkinson’s disease. Multiple system atrophy does not usually occur in families, indicating that genetic causes are rare. Multiple system atrophy is more difficult to diagnose clinically and has a more rapid progression compared to Parkinson’s disease. There are currently no effective therapies for multiple system atrophy.

Many of our research projects are aimed at understanding the cellular and tissue changes occurring in multiple system atrophy in order to identify better biomarkers and treatment targets for this rapidly progressing disease.




Progressive supranuclear palsy (PSP) is characterised by symptoms similar to Parkinson’s disease but is caused by a different protein depositing in the brain known as tau. One of the symptoms that is more characteristic of PSP is an inability to control eye movements, although this often occurs later in the disease. There are currently no effective therapies for PSP.

The exact causes of PSP are largely unknown, although in a very few number of families there is a tau gene abnormality. The deposition of the tau protein in everyone with this disease indicates that changes in the cellular processing of this protein are likely to be important. Many of our research projects are aimed at understanding the cellular and tissue changes occurring in PSP in order to identify better biomarkers and treatment targets for this progressive neurodegenerative disease.