Prof Glenda Halliday


Conjoint Senior Principal Research Fellow, NeuRA (2003 – 2018) Director, Sydney Brain Bank, UNSW and NeuRA (2008 – 2018)
Senior Principal Research Fellow, NHMRC (2010 – 2019)
Professor of Neuroscience, School of Medical Sciences, UNSW Medicine (2008 – 2018)

Prof Glenda Halliday is an Australian Professor of Neuroscience leading a research program of ~70 researchers tackling non-Alzheimer’s neurodegeneration that stems from her work on frontotemporal and motor neurodegenerative syndromes, and Parkinson’s disease. She is also Director of the Sydney Brain Bank. She received her degrees at University of New South Wales, and postdoctoral training at Flinders University prior to an ARC Queen Elizabeth II Fellow and NHMRC research fellowships since 1988, joining NeuRA in 1993. She has published >300 research papers and 2 books, and attracted >$30m in grant funding. Prof Halliday is on the editorial boards of 5 international journals, on Scientific Advisory Boards for 3 research institutes (one international), and is a committee member for a number of international organisations, including the International Brain Research Organization (a member organization of UNESCO). She was elected president of the Australian Neuroscience Society (ANS 2006-2007), awarded the 2011 ANS Nina Kondelos Prize, and named a high achiever in Australian Health and Medical Research by NHMRC.

Projects Prof Glenda Halliday is currently involved with


Alzheimer’s disease

This project focuses on how pathology spreads during disease progression, the link between amyloid-β (Aβ) and tau pathology, and down-stream mechanisms of Aβ- and tau toxicity.


Alzheimer’s disease

Parkinson’s disease

Investigating whether SNCA genetic variation relates to pathological variation in Parkinson’s disease
Mutations in the SNCA gene (encoding alpha-synuclein) cause autosomal dominant forms of Parkinson’s disease. This project aims to determine whether generic variation in SNCA relates to pathological severity of inclusion pathologies and alpha-synuclein protein levels.

With Dr Scott Kim (SRO)
The major focus of these projects is to understand the role of lipid dysfunction in Parkinson’s disease and the related disorder of multiple system atrophy. Increasing evidence shows that lipids regulate a number of neurodegenerative processes.

Understanding the role of lipids in alpha-synuclein aggregation process in parkinsonian syndromes
We have recently produced compelling evidence showing that lipid levels are significantly altered in disease-affected regions of parkinsonian syndromes. This project aims is to determine how lipids regulate alpha-synuclein aggregation process in parkinsonian syndromes.

Determining the role of COQ2 in multiple system atrophy pathogenesis
Myelin is a specialised lipid membrane that encases the axons of all neurons in the brain and is made by oligodendrocytes. These cells do not properly make myelin and degenerate in certain brain regions in multiple system atrophy. Without myelin neurons eventually die. Genome-wide association studies indicate that COQ2 is associated with an increased risk for multiple system atrophy. The aim of this project is to determine the role of COQ2 in the pathogenesis of multiple system atrophy.

With Dr Nicolas Dzamko (RO)
The major focus of these projects is to understand how mutations in certain genes cause inherited forms of Parkinson’s disease and whether/how these genes also contribute to non-inherited (sporadic) Parkinson’s disease. A particular focus is on leucine-rich repeat kinase 2 (LRRK2), a promising therapeutic target for Parkinson’s disease.

Measuring LRRK2 by flow cytometry
The LRRK2 protein is highly expressed in white blood cells. The aim of this project is to establish a flow cytometry assay to measure LRRK2 protein in white blood cells from Parkinson’s disease patients. This assay could then be used to monitor LRRK2 in any clinical trials using drugs to block LRRK2 function.

Effect of LRRK2 mutations on PD-associated inflammation
Inflammation is a common feature of Parkinson’s disease and LRRK2 is involved in the regulation of inflammation. This project aims to measure inflammatory markers in the serum and cerebrospinal fluid of subjects that have LRRK2 mutations but not yet Parkinson’s disease. We will determine if inflammation occurs early in the disease process and whether certain inflammatory markers can be used to predict Parkinson’s disease before clinical symptoms.

LRRK2 expression in brain
LRRK2 is promising drug target for the treatment of Parkinson’s disease. This projects aims to understand what happens to LRRK2 in the brain of Parkinson’s patients. This information will aid drug development and clinical trials for LRRK2 inhibitors.

LRRK2 and idiopathic Parkinson’s disease
Pathogenic mutations in LRRK2 cause inherited Parkinson’s disease but polymorphisms in LRRK2 are also a risk factor for sporadic Parkinson’s disease. This project aims to measure LRRK2 protein and its function in sporadic Parkinson’s disease patients. Results from this work will help determine if LRRK2 blocking drugs will be beneficial for all forms of Parkinson’s disease.

LRRK2 and type-1 interferon
We have established that LRRK2 is involved in inflammatory pathways that regulate interferon production. This project will generate and utilise state-of-the-art cellular models (induced pluripotent stems cells and crispr/cas9 genome editing) to understand how Parkinson’s disease-causing LRRK2 mutations affect inflammation.

TLR2 and the pathological spread of alpha-synuclein
The accumulation of insoluble alpha-synuclein protein is a hallmark feature of brain tissue from Parkinson’s patients. Recent evidence suggests that alpha-synuclein may spread through the brain in a prion-like manner, contributing to neurodegeneration. This project aims to determine the contribution that the toll-like receptor 2 (TLR2) makes to the spread of alpha-synuclein through the brain.

The association of VPS35 and pathological alpha-synuclein
Mutations in VPS35 are a rare cause of inherited Parkinson’s disease. Recent evidence suggests that VPS35 mutations may contribute to the accumulation of alpha-synuclein protein. This project aims to determine the association between VPS35 and alpha-synuclein in human Parkinson’s disease brain and to use cellular models to define this relationship.

Implications of neuronal toll-like receptor activation for Parkinson’s disease
Neuroinflammation contributes to cell death in Parkinson’s disease but how and via which pathways is mostly unknown. This project uses cell models to determine the contribution of the major inflammatory regulating toll-like receptor (TLR) pathway to neuroinflammation, with a particular focus on the largely unexplored role of TLR signalling in neurons.


Parkinson’s disease and related syndromes

Frontotemporal dementia and motor neurone disease

This project’s objective is to develop cell culture and mouse models to study underlying pathomechanisms and develop/test new treatments.


Frontotemporal dementia and motor neurone disease


Scott Kim

DR SCOTT KIM Senior Research Officer : +612 9399 1084

DR NICOLAS DZAMKO Research officer

Rachel Tan

DR RACHEL TAN Research officer

Heidi Cartwright

HEIDI CARTWRIGHT P/T Senior Research Assistant

Gayathri Perera

GAYATHRI PERERA Research assistant


Neuropathology of α-synuclein propagation and braak hypothesis.

McCann H, Cartwright H, Halliday GM

Parkinson's disease is a progressive neurodegenerative disorder with multiple factors contributing to increasing severity of pathology in specific brain regions. The Braak hypothesis of Lewy pathology progression in Parkinson's disease proposes a systematic spread of α-synuclein that can be staged, with the later stages correlating with clinical aspects of the disease. The spread of pathology through the different stages suggests progression, a theory that has proven correct from evidence of pathology in healthy neurons grafted into the brains of patients with Parkinson's disease. Progression of pathology occurs on a number of levels, within a cell, between nearby cells, and then over longer distances throughout the brain, and evidence using prion proteins suggests two dissociable mechanisms-intracellular toxicity versus a nontoxic infectious mechanism for propagation. In Parkinson's disease, intracellular changes associated with mitochondria and lysosome dysfunction appear important for α-synuclein propagation, with high stress conditions favoring mitochondrial cell death mechanisms. Functional neurons appear necessary for propagation. Unconventional exocytosis releases α-synuclein under stress conditions, and endocytic uptake occurs in nearby cells. This cell-to-cell transmission of α-synuclein has been recapitulated in both cell culture and animal models, but the timeframe of transmission is considerably shorter than that observed in transplanted neurons. The time course of Lewy pathology formation in patients is consistent with the long time course observed in grafted neurons, and the restricted neuronal loss in Parkinson's disease is potentially important for the propagation of α-synuclein through relatively intact circuits. © 2015 International Parkinson and Movement Disorder Society.

The substantia nigra and ventral tegmental dopaminergic neurons from development to degeneration.

Fu Y, Paxinos G, Watson C, Halliday GM

Increased peripheral inflammation in asymptomatic leucine-rich repeat kinase 2 mutation carriers.

Dzamko N, Rowe DB, Halliday GM

The results suggest that peripheral inflammation is higher in a percentage of subjects carrying the LRRK2 G2019S mutation. Replication and longitudinal follow-up is required to determine whether the increased peripheral cytokines can predict clinical PD. Importantly, these biological changes were observed prior to the clinical manifestations thought to herald PD. © 2016 International Parkinson and Movement Disorder Society.

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