Biomarkers and Neuropathology Lab- Halliday Research Group

Lab head: Prof. Glenda Halliday
Location: Brain & Mind Ctr, Mallet St Campus. 97 Church St, Camperdown NSW 2050

Understanding the common and unique pathomechanisms in dementia with Lewy bodies, Parkinson’s disease and Alzheimer’s Disease

Primary supervisor: Siva Purushothuman

Synopsis: Dementia with Lewy bodies (DLB) is the second most common type of dementia, accounting for 10-15% of all dementia cases. Patients with DLB often have common clinical symptoms with Alzheimer’s and Parkinson’s diseases, but also develop other distinct early symptoms. This may lead to some confusion in clinical diagnosis and management of DLB.

Lysosomes: Lysosomes are dynamic organelles that degrade cellular components delivered to them in a controlled manner via the secretory, endocytic, autophagic and phagocytic membrane-trafficking pathways. Increasing evidence suggests a central role of lysosomal impairment in most neurodegenerative diseases, as dysfunction of lysosomes leads to the accumulation of unwanted molecules in cells. Such accumulations are obvious in the brain in diseases such as Alzheimer’s disease (AD, accumulates beta-amyloid and tau proteins) and Lewy body diseases (e.g. Parkinson's disease & dementia with Lewy bodies) accumulate α-synuclein  as well as in other neurodegenerative conditions. It is thought that specific defects in distinct lysosomal pathways underpin the variety of different neurodegenerative conditions

Synaptic and cytoskeletal changes: Cytoskeletal changes are obvious in AD in the form of microtubule associated protein tau deposition. The less obvious synaptic loss is the best current pathogenic correlate of cognitive decline. However, neurofilament abnormalities have not been assessed in detail across these disorders, although they are known to be associated with Lewy body and neurofibrillary tangle formation.

Inflammation in CNS: There is an increasing body of literature suggesting glial cells play a central role in AD and Lewy body disease progression. Data also show that these cells are important for the maintenance of neuronal, vascular and synaptic integrity as well as their immune functions. 

Overall Aim: To identify the common and differentiating factors and cellular mechanisms in the different cohorts of patients

The project will utilize the readily available brain samples from the Sydney Brain bank that are kindly donated by brain donors. This project has all the material and ethics approval, and would be achievable in the timeframe at Honours level. The student(s) will further enhance the knowledge in Neuroanatomy and Pathology with Molecular Biology and histology techniques.

Possible Projects:

1) Assess the lysosomal, apoptotic and mitochondrial protein changes 

2) Assess the changes in inflammatory cells, including growth factors

3) Assess the cytoskeletal and synaptic changes

4) Assess the levels of proteins such as amyloid-beta, tau, synucleins and lipoproteins

Discipline: Pathology
Co-supervisors: Woojin Kim
Keywords: Pathogenesis, Parkinson's disease, Alzheimer's disease