Frontotemporal dementia


Understanding the brain changes involved in frontotemporal dementia


Common causes

The brains of people with frontotemporal dementia show a severe loss of brain cells (neurons). In some individuals protein known as ‘tau’ collects in neurons known as ‘Pick bodies’. More commonly, the brains of people with FTD shows an accumulation of another cell protein called ubiquitin. Very recent research has suggested that the accumulation of ubiquitin is attached to another protein called TDP-43, which has a fundamental role in the nuclei of brain cells.

In frontotemporal dementia, as the name suggests, these changes may be present in the frontal lobes, the temporal lobes or both. As the disease progresses these brain regions show shrinkage.

Almost a third of patients with FTD have a family history of dementia, if you include relatives with any sort of dementia coming on at any age. True familial FTD, however, is much rarer, accounting for about 10 -15% of cases. The genetic basis of FTD is not fully understood and is a topic of active research.

About our research

ForeFront, is an amalgamation of three Australian government funded research groups: the NHMRC Frontotemporal Dementia (FTD) and Motor Neuron Disease (MND) program grant, the NHMRC Dominantly Inherited Non-Alzheimer Dementias team grant and the memory node of the ARC Centre of Excellence in Cognition and Its Disorders. This represents a unique bringing together of clinical and laboratory-based researchers dedicated to unravelling the mechanisms underlying FTD and MND and to developing effective therapies. Several investigator groups at NeuRA are involved in ForeFront (Halliday, Hodges, Piguet, Kwok, Ittner), in addition to research groups at Macquarie University and the Universities of Sydney, Queensland and Melbourne.

What we have discovered

Over the last two years, the ForeFront group has:

  • Identifed how the pathology spreads in the brain.
  • Identified that white matter and axonal degeneration are early and very progressive events.
  • Identified that genes and nonpharmacological interventions that increase glial activity in the brain ameliorate clinical phenotypes.
  • In FTD specifically, identified that phosphorylation of tau protein is most important for disease effects in tauopathies.

Assessing whether the main proteins differ in the toxicity and mechanisms of action:

  • Identified early axonal damage only in FTD with tau and not TDP-43 pathologies.
  • Genetic factors that induce TDP-43 pathology and factors related to eating and metabolism appear to combine to influence the progression of dementia and MND.

Identifying the patients with different brain proteins:

  • Established rapid new gene and blood screening techniques.
  • Identified clinical predictors of pathology within different clinical FTD syndromes.
  • Identified neuroimaging and genetic factors within different clinical FTD syndromes.

Treatment development and clinical trials:

  • In animal models of dementia, identified two nonpharmacological approaches to ameliorate brain pathology identifying that the repeated scanning ultrasound method activates.
  • Microglia to clear amyloid and improve performance without causing overt damage
  • In animal models of FTD, identified that passive immunization can therapeutically ameliorate tau pathology.
  • In animal models of FTD and MND, identified a number of potential new therapeutic targets
  • In animal and human studies of FTD, identified low progesterone levels in certain FTD subtypes that can ameliorate disease.
  • In clinical trials for FTD, identified that sustained memory enhancement can be achieved with cognitive intervention.
  • In clinical trials for FTD, we are one of three Australian sites in a ~70 site multinational Clinical Study TRx-237-007 (a Phase III Study of TauRx in behavioiural variant frontotemporal dementis) sponsored by TauRx Therapeutics and is fully recruited to treat patients for 52 weeks (due June 2016).
  • In clinical trials for MND, was the lead Australian site for the GSK-sponsored study NOG112264 (a Phase II Study of Ozanezumab (GSK1223249) versus Placebo in the Treatment of MND).


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