Project - Understanding immune pathways altered in frontotemporal dementia and amyotrophic lateral sclerosis (2018-2021)
Research Project Description
Frontotemporal dementia (FTD) is a group of neurodegenerative diseases characterised by behaviour and language alterations. The most common subtype is behavioural variant FTD (bvFTD). Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease characterised by muscle wasting. Genetic, molecular and clinical evidence suggest that these two diseases lie on the same disease spectrum. Neuroinflammation is known to be widely present in both bvFTD and ALS and exacerbate disease pathology. Currently there is a lack of effective biomarkers for both diseases. Understanding immune related proteins may better understand disease pathology and allow for the discovery of better bvFTD and ALS biomarkers. In order to address this my project includes: (1) Proteomics screen of bvFTD, ALS and control human serum and validation of any changes. Techniques used include mass spectrometry, statistics, gene ontology, western blotting and ELISA.
(2) Cytokine screen of bvFTD, ALS and control human serum samples and bvFTD and control human brain tissue samples. Techniques include protein fraction extraction, multi-plex ELISA and statistics. (3) Quantification of ABCA transporter expression in FTD and control human brain tissue and correlation to immune markers. Techniques include RNA extraction, qPCR, protein fraction extraction, western blotting. By examining central and peripheral changes, this research hopes to identify new molecular pathways altered in bvFTD and ALS that both furthers understanding of the pathological process and identifies potential biomarkers to aid diagnostics and therapeutic interventions.
Key Publications from this project
- Phan K, He Y, Pickford R, Bhatia S, Katzeff JS, Hodges JR, Piguet O, Halliday GM, Kim WS. Uncovering pathophysiological changes in frontotemporal dementia using serum lipids. Sci Rep 10, 3640 (2020)
- Katzeff JS, Bright F, Lo K, Kril JJ, Connolly A, Crossett B, Ittner LM, Kassiou M, Loy CT, Hodges JR, Piguet O, Kiernan MC, Halliday GM, Kim WS. Altered serum protein levels in frontotemporal dementia and amyotrophic lateral sclerosis indicate calcium and immunity dysregulation. Sci Rep 10, 13741 (2020)