Research outline -
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The main research interests of this Unit are the pathogenesis of neurological and psychiatric disorders. We have research projects studying neurodegenerative disease, such as Alzheimer’s disease, frontotemporal dementia (FTD), motor neuron disease (MND) and Lewy body diseases, as well as alcohol-related brain damage, schizophrenia and brain tumours. Using a variety of histological and molecular techniques we aim to understand the clinicopathological correlations of central nervous system diseases and the role of genes in the causation of these diseases.
Research in Dementia, Neurodegeneration & Ageing - Professor Jillian Kril
The neuropathology of ageing and dementia
The main thrust of this research is to elucidate the topography and extent of brain pathology during ageing and in patients with dementia. Little is known about why certain brain regions and certain neuronal populations are susceptible to damage in dementia. Prof Kril and colleagues are investigating the extent and pathogenesis of neurodegeneration in Alzheimer’s disease (AD), frontotemporal dementia (FTD), vascular dementia (VaD) and other types of dementia.
An important feature of this research is the inclusion of well-characterised, longitudinally followed patients and controls. This is made possible through collaborations with neurologists, geriatricians and other specialists who perform assessments on patients enrolled in research studies. They are then invited to join a brain donor program by agreeing to the examination of their brain after death. This program is run in collaboration with Prof Glenda Halliday, Prof John Hodges and colleagues at Neuroscience Research Australia.
Frontotemporal dementia (FTD) accounts for 12-20% of all dementia and is as prevalent as ALzheimer's disease (AD) in the <65y age group. However, our understanding of FTD lags far behind that of AD and current diagnostic criteria are without validation and show low specificity, compromising research efforts. This, in part, is due to the finding that FTD is a spectrum of disorders with a number of clinical phenotypes, and unlike other neurodegenerative disorders, which show a high degree of clinical homeogeneity.
The cause of FTD is unknown, although in a small proportion of cases gene mutations have been identified. In addition to the clinical subtypes, there are also a number of pathological subtypes of FTD. On-going studies in collaboration with clinical researchers, are aimed at elucidating the relationship(s) between the clinical and the pathological subtypes of FTD. We have shown that, while ther are a number of trends, there is not a direct relationship between the clinical and pathological phenotypes for most subtypes of FTD. This project aims to find better ways of identifying and diagnosing FTD and FTD subtypes during life and at postmortem.
The group is also working on understanding the neuropathological substrate of the cognitive deficits seen in patients with FTD. By comparing groups of patients with different patterns or severity of cognitive disorders a better understanding of the neural circuits which underlie these functions and how they are disturbed in neurodegenerative diseases will be achieved.
Small vessel cerebrovascular disease and its relationship to neurodegeneration
Magnetic resonance imaging (MRI) often reveals areas of high signal intensity in the cerebral white matter of elderly people. These lesions are known as white matter hyperintensities (WMHs) and have been associated with numerous disorders including cerebrovascular disease, dementia and gait disturbances. Despite a variety of investigations into this phenomenon, the pathogenesis of WMHs remains unknown and their contribution to the clinical and pathological phenotype of elderly patients is unclear. Futhermore, the group continues to investigate the pathological features of small vessel disease and what role it has in the pathogenesis of a number of disorders including dementia and Parkinson's disease.
Alcohol related brain damage
In collaboration with Dr Greg Sutherland Prof Kril is investigating neurogenesis in the alcoholic brain. Evidence from rodents suggests that chronic alcohol consumption impairs brain neurogenesis, but it is unclear whether this is the case in humans, or indeed whether significant neurogenesis occurs in older adult brains.
Motor Neuron Disease Research - Associate Professor Roger Pamphlett
The aim of the Motor Neuron Disease Research Group is to find the cause of sporadic Motor Neuron Disease, a disease that kills one Australian every day. Motor Neuron Disease (also known as ALS) causes progressive muscle weakness, and leads to death usually between two to five years after diagnosis. No curative treatment is available. In 90% of patients the disease affects only one member of a family.
The research team in the Stacey Motor Neuron Disease Laboratory at the University of Sydney is investigating a number of possible causes of Motor Neuron Disease, using DNA and tissue samples obtained from both the Australian Motor Neuron Disease DNA Bank and the Australian Brain Bank Network.
For a list of recent research publications from the Stacey Motor Neuron Disease Laboratory, please enter “neuron pamphlett r” in the search box of PubMed (www.ncbi.nlm.nih.gov/PubMed), then click “Display Settings” and Sort by “Pub Date”.
The Australian Motor Neuron Disease DNA Bank
This Bank, funded by an Enabling Grant from the NHMRC and situated at the University of Sydney, has been collecting blood DNA samples from people with Motor Neuron Disease, as well as from controls, for over 5 years. The Bank now contains almost 3,000 DNA samples from people in all the states of Australia. The Bank will not be collecting samples from new donors after June 2011. For any enquiries about this Bank, please contact Dr Roger Pamphlett at .
Molecular Neuropathology - Dr Michael Buckland
The Molecular Neuropathology laboratory operates in the Department of Pathology, University of Sydney and is run by Dr Michael Buckland. It is closely affiliated with the Department of Neuropathology at Royal Prince Alfred Hospital, Sydney.
Research in the laboratory focuses on brain tumours (gliomas) and schizophrenia.
Brain tumour research
Brain cancer is a common, devastating disease. Most primary brain tumours are gliomas, and in adults are mostly incurable and fatal. In NSW, by 2011, the incidence of gliomas is predicted to rise by 18 per cent (NSW Cancer Institute Media Release 18/3/2005). The laboratory’s researchers are investigating the morphological and molecular underpinnings of human gliomas to improve their diagnosis and treatment .
Schizophrenia is a chronic, crippling disease which affects up to 1 in 100 Australians. It ravages not only those affected but also their families.
Subtle physical brain abnormalities in persons afflicted with schizophrenia suggest an organic underpinning to the disease, and the tendency for schizophrenia to run in families suggests genetic or epigenetic inheritance. Our project investigates the possible role of small non coding RNAs in schizophrenia.
- NHMRC Project Grants - Pathogenic mechanisms common to all subtypes of frontotemporal dementia. Kril J, Ittner L, Goetz J, Halliday G. $491,250
Visit the Academic Researcher Profiles for a current list of Publication Citations.