Our trainees review webinars in their given fields and share abstracts to help colleagues outside their discipline make an informed choice about watching them. As our program bridges diverse disciplines, these abstracts are beneficial for our own group in helping one another gain key knowledge in each other’s fields. We are happy to share these here for anyone else who may find them helpful.
Unlocking the elusive mind: The role of protein biomarkers in understanding neurodegenerative disease
Douglas R. Galasko, M.D. University of California San Diago
Henrik Zetterberg, M.D., Ph.D. University of Gothenburg, Sweden
Kaj Blennow, M.D., Ph.D, University of Gothenburg and Sahlgrenska University Hospital
Millions of people suffer from neurodegenerative diseases with Parkinson’s and Alzheimer’s being the most reported. Accurate diagnosis of these diseases is very essential in any attempt to provide therapeutic interventions for these patients.
This webinar discusses several approaches to detecting protein biomarkers of neurodegenerative disease and their potential roles in disease progression. Dr. Kaj Blennow, a professor at the University of Gothenburg, kicked off this webinar by giving a background on Alzheimer’s disease. In brief, he discussed the occurrence of beta-amyloid plaques and phosphorylated tau protein tangles in hippocampal neurons of Alzheimer’s disease patients as well as the possible mechanism leading to the formation of these plaques and tangles. Further, he hinted at other factors that can lead to neuronal degeneration and how they can affect Alzheimer’s diagnosis.
Dr. Blennow also talked about the relative levels of beta amyloids and phosphorylated tau proteins in cerebrospinal fluids and plasma of Alzheimer’s disease patients and healthy individuals measured by enzyme-linked immune assay (ELISA). The levels of phosphorylated tau proteins were determined to be two hundred times higher in the CSF of Alzheimer’s patients when compared with healthy individuals whereas beta-amyloid concentration was low in Alzheimer’s patients. However, no significant difference was observed in the concentration and phosphorylated tau in Alzheimer’s and healthy patients in plasma samples, although beta amyloids seem to be a promising plasma biomarker for Alzheimer’s disease as they recorded low levels in Alzheimer’s patients than the healthy cohorts. He also discussed how neurofilament L (NFL), a cytoskeleton protein, can serve as a possible biomarker for Alzheimer’s disease since they observed a significant difference in the concentration of NFL between the two groups for both CSF and plasma samples.
Mass spectrometry remains the state-of-the-art instrument in proteomics; nevertheless, it is expensive and cannot be easily adopted in clinical laboratories. In this webinar, Dr Douglass Galasko discussed a multiplex approach to detecting protein biomarkers for neurodegenerative disease base on proximity extension assays. The assay is based on oligonucleotides linked to antibodies that target specific proteins. Briefly, antibodies for specific proteins are linked to two different oligonucleotides that hybridize only when in proximity (when bound to the target). Hybridized oligonucleotides are extended and amplified, making them adequate for less concentrated samples. The assay can be multiplexed by using DNA barcodes or different sequences for different antibody targets. By employing this analytical approach, 331 out 460 analytes in a sample were detected. The procedure was extended to measure protein biomarkers in CSF of Alzheimer’s disease and healthy patients. CD200, WIF1, ROBO2, and PRSS27 were among the proteins determined to be possible biomarkers of Alzheimer’s disease using this technique. Overall, protein levels were observed to be lower in Alzheimer’s patients than in healthy individuals.
Dr. Henrik Zetterberg, of the University of Gothenburg, discussed the differences in the levels of inflammatory biomarkers in patients with multiple sclerosis, Alzheimer’s, Parkinson’s, and healthy individuals. Using proximity extension assay for inflammatory biomarker measurement, no significant difference was observed in the concentration of the inflammatory proteins between healthy, Alzheimer’s, and Parkinson’s disease; however, a remarkable difference in inflammatory biomarkers was observed for the patients with multiple sclerosis.
In summary, this webinar presents different alternatives in multiplex protein biomarker measurement as well as the occurrence of different biomarkers for neurodegenerative disease with potential clinical applications.