Catherine Blizzard

Changes to synapses - the specialised structures that allow neurons to communicate with each other – may be an early disease-causing event in Frontotemporal Dementia (FTD). TDP-43, a DNA processing protein, is one of the main proteins that have been identified to play a role in FTD.  There is now convincing evidence that the dysfunction of TDP-43 can lead to the synaptic disturbances.  Her fellowship aims determine how TDP-43 changes lead to synaptic alterations, through in vitro primary culture techniques and a unique mouse model with sophisticated in vivo live imaging techniques, coupled with post mortem human FTD brain investigation.

Frontotemporal dementia (FTD), a presenile dementia second only to Alzheimer’s in prevalence, is caused progressive neuronal atrophy in the frontal and temporal cortices causing personality and behavioural changes. Despite the high incidence of FTD, in persons under the age of 65, relatively little is know about the pathogenic events leading to cognitive decline. FTD can be pathologically characterised by the cytoplasmic accumulation of aggregated proteins causing a loss of functional protein.  One such protein is the transactive response DNA-binding protein 43 (TDP-43).  TDP-43 actively regulates synaptic strength in dendritic spines. Recent research and our own preliminary investigations implicate TDP-43 pathogenesis in the synaptic dysfunction in FTD.  

For this Alzheimer’s Australia post-doctoral fellowship Catherine will use human tissue, transgenic models and in vivo live imaging to investigate the novel hypothesis that ‘miss-processing of TDP-43 results in dendritic spine and synaptic alterations in the cortex, leading to impaired neuroplasticity and FTD’. Determining the cellular mechanisms underlying TDP-43’s role in cortical pathogenesis is the critical first step towards potential clinical interventions targeting synaptic plasticity and spine homeostasis to improve outcomes for people suffering from FTD.

Dr Blizzard is a Postdoctoral Research Fellow at the Menzies Institute for Medical Research, University of Tasmania. Her two year half funded AADRF fellowship began in early 2014.

Dr Blizzard was also named as a 2013 Tasmanian state finalist for the Young Australian of the Year Awards, recognising her work in the field of neuroscience.