Dr Rachel Tan

Dr Rachel Tan, NHMRC-ARC Dementia Research Fellow, The University of Sydney.

Rachel is a Senior Research Fellow at The University of Sydney with skillsets in neuropathology, neuroimaging, genetics and molecular biology. Her research focuses on identifying and understanding the various pathomechanisms involved in motor neuron disease and frontotemporal dementia; the clinical features associated with these distinct pathways; and clinical markers that can improve the early and accurate identification of patients with these.

Prior to commencing her research in neurodegenerative disorders, Rachel trained at the University of Melbourne. Her PhD developed a novel hair-root assay for the detection of mutations in patients with inherited nephritis; and studied the use of chemical chaperone drugs to prevent protein misfolding in cell lines developed from these patients with identified mutations.

Forefront Group:

  • BMC DAMD Frontotemporal Dementia Research Group
  • BMC DAMD Motor Neurone Disease Research Group

Affiliate Organisations

USyd, BMC

Neurodegeneration of interest:

Motor Neuron Disease, Language and behavioural Frontotemporal Dementia

Expertise:

Neuropathology

Specific Skills:

Medical Scientist

Projects:

  • Prions, RNA binding proteins with prion-like domains and motor neuron degeneration (CIA)
  • Dual and multiple proteinopathies in neurodegenerative dementias – risk factors, prognostic indicators and clinical ramifications (CIA)

Project - Prions, RNA binding proteins with prion-like domains and motor neuron degeneration

All Chief investigators and associate investigators

Rachel Tan (CIA)

Research Project Abstract

The prion protein in its normal form (PrPC) is widely expressed in the central nervous system. Importantly, emerging evidence demonstrates that PrPC is involved in the accumulation and spread of misfolded proteins that cause neuronal death. In Motor Neuron Disease (MND), the death of motor neurons has been linked to the accumulation of proteins that bear a prion-like domain. However, the relationship between PrPC and these proteins have not been studied. This project will assess this in tissue from patients with MND, with the purpose of determining whether targeting PrPC is a viable therapeutic strategy for sporadic MND. 

Project - Dual and multiple proteinopathies in neurodegenerative dementias – risk factors, prognostic indicators and clinical ramifications

All Chief investigators and associate investigators

Rachel Tan, Glenda Halliday

Research Project Abstract

"Dementia" is an umbrella term used to describe a group of neurodegenerative diseases, each subserved by distinct histopathological signatures of insoluble protein aggregates and spread. Converging evidence now indicates the overlapping deposition of pathologic proteins in at least 50% of dementia syndromes. The deposition of dual/multiple proteinopathies impacts on dementia symptoms and severity, and has important clinical implications for diagnosis and development of substrate-specific interventions, particularly since targeting and alleviating on proteinopathy without the other is unlikely to successfully ameliorate dementia in affected patients. Crtically, the prevalence and clinical ramifications of dual/multiple proteinopathies remains largely unknown. The present study will assess cases from the Sydney Brain Bank, which holds tissue from >650 patients with a pathologically-confirmed clinical dementia syndrome, with the purpose of determining the prevalence and clinical ramifications of dual/multiple proteinopathies in neurodegenerative dementias.

Project - Histopathological changes in MND and FTD

Disease areas:

Motor Neuron Disease (MND) and Frontotemporal Dementia (FTD)

Research Project Description

Motor Neuron Disease (MND) is a rapidly progressive and debilitating neurodegenerative disorder caused by the death of motor neurons that enable us to move, breathe and swallow. MND occurs sporadically in ~90% of patients and the average survival is 2.5 years from symptom onset. There is currently no cure for MND, with available therapies only able to prolong life expectancy by 3 months. Cognitive and neuropsychiatric symptoms are common and ~20% of patients are also clinically diagnosed with frontotemporal dementia (FTD).

Aberrant TDP-43 protein accumulates in vulnerable neuronal populations of affected brain regions in patients with MND and FTD. By studying the characteristics and patterns of this TDP-43 protein in postmortem brain tissue from patients, we are able to further understand the underlying causes of the behavioral, language and motor symptoms in MND and FTD. This is critical in order to advance drug discovery for the treatment of patients with MND and FTD.

Research Project Related Links

Further reading on the pathology of ALS and FTD can be found here – https://www.ncbi.nlm.nih.gov/pubmed/28058507