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Following completion of his BSc in Neuroscience and Psychology, Andrew completed his Master of Philosophy (Medicine) from the University of Sydney (2012). Since this time, he has gained further experience in neuroscience research and histopathology, working for the Bosch and Kolling Institutes and as a Scientific Officer for Healthscope Pathology. He is now a Research Associate employed by the Faculty of Medicine at the University of New South Wales. This is a junior academic associate lecturer level position that is based within the Sydney Brain Bank at Neuroscience Research Australia (NeuRA).
Andrew is responsible for organizing and performing brain and spinal cord removal from consented donors at the time of death and carrying out the macroscopic examination and dissection of both fresh and fixed tissue. He also performs a histopathological analysis of the brain tissue, which is essential for case characterization and classification. Through his work at the Sydney Brain Bank, Andrew is also involved in neuropathological research studies to improve the accuracy, reproducibility and efficiency of characterising brain tissue changes.
Andrew is also a part-time PhD candidate. His PhD project seeks to understand what effect anti-hypertensive medications may have on the brain pathology associated with Alzheimer’s disease and the reasons why such medications could be effective. Of particular interest is whether these medications have a direct effect on receptors in the brain tissue, or whether they affect the flow of blood to the brain. This study could provide specific drug recommendations for the prevention and treatment of Alzheimer’s disease.
The pathological sequestration of TAR DNA-binding protein 43 (TDP-43, encoded by TARDBP) into cytoplasmic pathological inclusions characterizes the distinct clinical syndromes of amyotrophic lateral sclerosis and behavioural variant frontotemporal dementia, while also co-occurring in a proportion of patients with Alzheimer's disease, suggesting that the regional concentration of TDP-43 pathology has most relevance to specific clinical phenotypes. This has been reflected in the three different pathological staging schemes for TDP-43 pathology in these different clinical syndromes, with none of these staging schemes including a preclinical phase similar to that which has proven beneficial in other neurodegenerative diseases. To apply each of these three staging schemes for TDP-43 pathology, the clinical phenotype must be known undermining the potential predictive value of the pathological examination. The present study set out to test whether a more unified approach could accurately predict clinical phenotypes based solely on the regional presence and severity of TDP-43 pathology. The selection of brain regions of interest was based on key regions routinely sampled for neuropathological assessment under current consensus criteria that have also been used in the three TDP-43 staging schemes. The severity of TDP-43 pathology in these regions of interest was assessed in four clinicopathological phenotypes: amyotrophic lateral sclerosis (n = 27, 47-78 years, 15 males), behavioural variant frontotemporal dementia (n = 15, 49-82 years, seven males), Alzheimer's disease (n = 26, 51-90 years, 11 males) and cognitively normal elderly individuals (n = 17, 80-103 years, nine males). Our results demonstrate that the presence of TDP-43 in the hypoglossal nucleus discriminates patients with amyotrophic lateral sclerosis with an accuracy of 98%. The severity of TDP-43 deposited in the anterior cingulate cortex identifies patients with behavioural variant frontotemporal dementia with an accuracy of 99%. This identification of regional pathology associated with distinct clinical phenotypes suggests key regions on which probabilistic pathological criteria, similar to those currently available for Alzheimer's disease and dementia with Lewy bodies, can be developed for TDP-43 proteinopathies. We propose and validate a simplified probabilistic statement that involves grading the presence of TDP-43 in the hypoglossal nucleus and the severity of TDP-43 in the anterior cingulate for the pathological identification of TDP-43 proteinopathy cases with clinical amyotrophic lateral sclerosis and behavioural variant frontotemporal dementia.
This study demonstrates a higher consistency across independent observers in the pathological subtyping of FTLD-TDP cases with the use of a pTDP43 antibody in comparison to the iTDP43 antibody, and corroborates the use of pTDP43 for pathological classification of FTLD-TDP cases.