Halliday Research Lab - Neurodegenerative Diseases

---

Current Appointments

Professor Glenda M Halliday

---

Current Research Projects

---

Research Staff

Other Academic Researchers:
Olivier Piguet, BPsych, MAHons, PhD, NHMRC Neil Hamilton Fairley Fellow
William Brooks, MBBS, BA, MPH, NHMRC Senior Research Officer
Wayne Reid, BAHons, MPsych, PhD, Senior Research Officer
Yue Huang, BM, MSc, PhD, NHMRC Research Officer
Greg Sutherland, BVetSc, PhD, NHMRC Research Officer

Other Research Staff:
Heather McCann, DipHealthSci, Laboratory Manager
Heidi Cartwright, BSc, Data Manager and Computer Illustrator
Michael Cartwright, BSc, Msc(Hons), Research Assistant and IT Support
Samuel Merriment BSc(BioMed), Laboratory Assistant
Naomi Cook, BScHons, Research Assistant
Julia Stevens, BScHons, Research Assistant

Postgraduate Students:
Christine Song, BScHons - The staging and severity of multiple system atrophy
Daniel Brooks, BScHons – Pathological correlates of cognition
Vanessa Young, MBBS, BScMed – Neuropathological correlates of white matter hyperintensities
Cindy Kersaitis, BScHons – Cellular pathology in frontotemporal dementia
Emma Schofield, BScHons – Cortical pathology in progressive supranuclear palsy

Undergraduate Students
Natasha Mevawalla - Dopaminergic neurons in the olfactory bulb in neurodegenerative diseases
Shilpi Yadav - Quantitative analysis of the dentate nucleus in progressive supranuclear palsy

---

Recent Publications

In Parkinson’s disease

Henderson JM, Rodriguez M, O'Sullivan DJ, Pell M, Benabid AL, Halliday GM (2004) Partial lesion of the thalamic ventral intermediate nucleus after chronic high frequency stimulation. Mov. Disord. 19:709-711.

Huang Y, Cheung L, Rowe DB, Halliday GM (2004) Genetic contributions to Parkinson’s disease. Brain Res. Rev. 46:44-70.

Meredith GE, Halliday GM, Totterdell S (2004) A critical review of the development and importance of proteinaceous aggregates in animal models of Parkinson’s disease: New insights into Lewy body formation. Parkinsonism & Related Disorders 10:191-202.

In dementia with Lewy bodies

Aarsland D, Ballard C, Halliday G (2004) Are Parkinson’s disease with dementia and dementia with Lewy bodies the same entity? J. Geriatr. Psychiatr. Neurol. 17:137-145.

Harding AJ, Das A, Kril JJ, Brooks WS, Duffy D, Halliday GM (2004) Identification of families with cortical Lewy body disease. Am. J. Med. Genet. 128B:118-122.

McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen-Mansfield J, Dickson D, Dubois B, Duda J, Feldman H, Gauthier S, Halliday G, Lawlor B, Lippa C, Lopez O, Machado J, O’Brien J, Payfer J, Reid W (2004) Dementia with Lewy bodies. Lancet Neurol. 3:19-28.ation of families with cortical Lewy body disease. Am. J. Med. Genet. B. Neuropsychiatr. Gen. in press.

In Alzheimer’s disease

Broe M, Shepherd CE, Mann DMA, Milward EA, Gai WP, Thiel E, Halliday GM (2004) Insoluble -synuclein in Alzheimer’s disease without Lewy body formation. Neurotox. Res. 7:69-76.

Brooks WS, Kwok JBJ, Halliday GM, Godbolt A, Rossor MN, Creasey H, Jones AO, Schofield PR (2004) Hemorrhage is uncommon in a new Alzheimer’s family with the Flemish amyloid precursor protein mutation. Neurology 63:1613-1617.

Gregory GC, Halliday GM (2004) What is the dominant A species in human brain tissue? Neurotox. Res. 7:29-41.

Shepherd CS, Gregory GC, Vickers JC, Brooks WS, Kwok JBJ, Schofield PR, Kril JJ, Halliday GM (2004) Positional effects of presenilin-1 mutations on tau phosphorylation in cortical plaques. Neurobiol. Dis. 15:115-119.

In frontotemporal dementia

Broe M, Kril J, Halliday GM (2004) Astrocytic degeneration relates to the severity of disease in frontotemporal dementia. Brain 127:2214-2220.

Hodges JR, Davies R, Xuereb J, Casey B, Broe M, Bak T, Kril J, Halliday GM (2004) Clinicopathological correlates in frontotemporal dementia. Ann. Neurol. 56:399-406.

Kersaitis C, Halliday GM, Kril JJ (2004) Regional and cellular pathology in frontotemporal dementia: Relationship to stage of disease. Acta Neuropathol. 108:515-523.

Piguet O, Brooks WS, Halliday G, Schofield PR, Stanford PM, Kwok J, Spillantini MG, Yankopoulou D, Nestor PJ, Broe GA, Hodges JR (2004) Similar early clinical presentations in familial and non-familial frontotemporal dementia. J. Neurol. Neurosurg. Psychiatry 75:1743-1745.

---

Possible Research Projects for Students

Longitudinal studies determining susceptibility and predictive factors for neurodegeneration in community dwelling elderly
Supervisors: Dr Hayley Bennett and Prof Tony Broe

During 1997-2000 127 community living persons aged 81 and over were neuropsychologically, neurologically, and functionally assessed, as well as undergoing Magnetic Resonance Imaging (MRI) of the brain. Three year review of these people is currently underway, with all assessments and investigations being repeated in 2002. A number of potential projects associated with this study are possible. These include:

• Identifying predictors of dementia with Lewy bodies in a community sample. This dementia syndrome has recently been recognised as the second most common form of dementia. Identifying any early differences between people destined to get this disease versus Alzheimer's disease will significantly improve the development of targeted drug therapies.
• Determine the involvement of white matter changes with cognitive decline in the elderly. There is only limited longitudinal data from elderly persons concerning the development of white matter abnormalities and their clinical relevance.
• Analyse the changes in hippocampal size and memory over time in the very elderly. Changes in these measures are thought to be indicative of Alzheimer's disease, although the evidence is still controversial in those over 80 years of age.
• Determine if there is any association with cerebellar size and longitudinal measures of gait and cognition. Many elderly people slow down or have some difficulty with mobility. The underlying substrate for this age related change is unknown, and therefore current treatment options are very limiting.

The involvement of the occipital lobe in dementia with Lewy bodies
Supervisors: Dr Antony Harding and A/Prof Glenda Halliday

Dementia with Lewy bodies is a relatively newly recognised prevalent dementia syndrome. We and others have found that it is unlike Alzheimer's disease in that the cortical tissue of the brain is well preserved, despite a florid dementia syndrome. Overseas studies consistently show decreased regional cerebral blood flow in the occipital lobe in people with dementia with Lewy bodies. However, we and others have also shown that the Lewy bodies characteristic of the disease are largely absent from this brain region, and therefore the reason for the change in blood flow in the occipital lobe is unknown. Using cases from the POWMRI Brain Bank this project will examine the occipital lobe in cases with dementia with Lewy bodies, to identify any structural reason for the hypoperfusion in this region, and determine the clinical relevance. This research will clarify pathogenic mechanisms in this disease.

Axonal transport in dementia with Lewy body disease
Supervisors: Dr Claire Shepherd and A/Prof Glenda Halliday

Recent experiments within our laboratory have demonstrated that neurofilament proteins abnormally accumulate in significantly more neurons than expected in dementia with Lewy bodies. Neurofilament proteins are a major constituent of the cytoskeleton and are important in the structure and function of both the cell soma and axon. As the soma appears largely unaffected in this disease, accumulations of these proteins may cause dysfunctional axonal transport mechanisms and explain the clinical dementia syndrome in the absence of significant cell loss. Understanding the role of dysfunctional axonal transport in dementia with Lewy bodies and its association with the clinical dementia syndrome will provide further insight in to the underlying cause of this neurodegenerative disease. Formalin fixed paraffin embedded brain tissue from a number of well-characterised cases will be studied using immunohistochemical techniques to identify and quantify proteins involved in axonal transport. Such advances in our understanding of the disease process will prove invaluable in the search for therapeutic strategies.

Glial associated tau in frontotemporal dementia
Supervisors: Dr Claire Shepherd and A/Prof Glenda Halliday

The tau protein is a microtubule associated protein that has been implicated in a number of neurodegenerative disorders. Tau can be classified into three or four repeat isoforms according to the number of microtubule binding domains contained within the protein, and certain isoforms aggregate in glia and neurons in different degenerative disorders. It was thought that the cellular aggregates in individuals were of the same isoform (seen in familial frontotemporal dementias), but more recent evidence has shown that different cell types in an individual have different isoforms (glia versus neurons in sporadic frontotemporal dementia with Pick's disease). This project will examine tau isoforms in brain tissue from diverse cases with frontotemporal dementia using immunohistochemical techniques. The aim is to identify the specific tau isoforms that are deposited in order to understand their role in the disease process.