Quick Project Snapshot
Uncovering the role of exosome derived lipids in Alzheimer’s disease.
Alzheimer’s disease (AD) is a progressive dementia affecting more than 40 million people worldwide. The lack of disease-modifying treatments and the knowledge that existing drugs offer only modest delays in symptom onset exacerbate the significant financial and emotional tolls that AD places on families and communities at large. A new approach to the study of Alzheimer’s disease is long overdue. In recent years, small extracellular vesicles released by the cell, called exosomes, have emerged as key players in neurodegenerative disease. Exosomes are important for two principal reasons, they contain a selection of proteins, RNA and lipids, which act as key players in cell-to-cell communication, and can be characterised to provide a snapshot of parental cell homeostasis.
The proposed project will access the wealth of lipidomic information contained within human brain exosomes. Lipids have been shown to play a fundamental role in influencing the various risk factors of AD and to be closely involved in the pathogenesis of AD. This will involve isolating and characterising exosomes from human control and Alzheimer’s disease brain. The aims are to afford the first lipid profile of brain derived exosomes and uncover the role of exosomal lipids in Alzheimer’s disease. The student will learn techniques including exosome isolation, western blotting, density gradients, electron microscopy and lipidomic profiling. This will be a collaborative research project with the Florey Institute of Neuroscience and Mental health and The University for Melbourne.
This project is co-supervised by Professor Gavin Reid at the Bio21 Institute
This laboratory has expertise in Medicinal Chemistry (in association with Prana Biotechnology) and in biomarker discovery. More recently, it has focussed on the pathways leading to Parkinson’s disease, especially around the oxidative modifications of tau.
The Australian Imaging, Biomarker and Lifestyle (AIBL) Study, the Dementia Collaborative Research Centres (DCRC) and the Cooperative Research Centre for Mental Health (CRCMH). AIBL, DCRC and the CRCMH are intimately involved in our research programs, relying on patient cohorts for biomarker and imaging discovery in both neurodegenerative and psychotic illness.
Translation of our research findings into clinical practice will become more important over the next five years, as we move from a series of failed or equivocal phase 3 drug trials sponsored by the pharmaceutical industry. There is now general agreement that these drug trials need to be based at the earliest possible stage of Alzheimer’s disease, hence our participation in the Dominantly Inherited Alzheimer Network (DIAN) and the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s disease (the A4 study). These two pre-clinical trials are designed to administer drugs in the preclinical phases of both familial and sporadic Alzheimer’s disease.
All Projects by this LabEffect of Abeta on excitotoxic signalling pathwaysEffect of tau phosphorylation on exosome release in cell culture systemsThe influence of alpha-synuclein on olfactionThe role of peroxinitrite in depressionThe role of tau protein in olfactory processesAre exosomes driving Alzheimer’s disease pathogenesis?Discovering how toxic proteins traffic from cell to cell in Alzheimer’s disease.Uncovering the role of exosome derived lipids in Alzheimer’s disease.
Dr Lachlan Thompson
Prof David Finkelstein
Scientists in the Neurodegeneration division interrogate how neurones live, die and can be rescued to improve brain function in degenerative conditions such as Parkinson’s and Motor Neuron Diseases. There is no effective treatment for Motor Neurone Disease and the incidence of Parkinson’s Disease is rising alarmingly in our aging community. Gene abnormalities, energy deprivation, toxic rubbish accumulation and inflammation all contribute to a toxic environment for brain cells. Our teams study these events in animal models and cultured cells, with a view to translating knowledge into new therapies for human patients.