Glycoproteomics of Human Sera for the Discovery of Biomarkers for Dementia

David Morgenstern, G-INCPM, Weizmann Institute of Science, Rehovot, Israel (david.morgenstern@weizmann.ac.il)
Nili Tickotsky, The Goodman Faculty Of Life Sciences, Bar Ilan University, Ramat Gan, Israel
Hila Wolf-Levy, G-incpm, Weizmann Institute Of Science, Rehovot, Israel
Itzik Cooper, Sheba Medical Center, Ramat Gan, Israel
Jaime Uribarri, Department Of Medicine, Icahn School Of Medicine At Mount Sinai, Nyc, Usa
Ron Unger, The Goodman Faculty Of Life Sciences, Bar Ilan University, Ramat Gan, Israel
Buchman Aaron S., Rush University Medical Center, Chicago, Usa
Yishai Levin, G-incpm, Weizmann Institute Of Science, Rehovot, Israel
Michal Schnaider Beeri, Sheba Medical Center, Ramat Gan, Israel

In the realm of preventative medicine, identification of biomarkers that will predict initiation of disease early enough, is highly desirable. More often than not, biomarkers that point to change in homeostasis tend to be “too late” for prevention. In proteomics, disruption of protein homeostasis tends to occur too late for prevention, while analysis of common signaling (i.e. phosphorylation) is too sensitive to short term changes.

Protein glycosylation is a posttranslational protein modification has the potential for being an excellent biomarker.  While glycosylation is very stable within individuals, it changes in composition due to physiological alterations, but will not be modified once the glycan chain has been synthesized making it less sensitive to short term changes.

Unfortunately, glycoproteomic profiling for biomarker discovery, has proved to be extremely difficult to perform, due to the sheer complexity of the glycoproteome, the level of expertise required for such analyses and immaturity of the analytical techniques for measuring it.

Here we show our novel method for glycopeptide enrichment that enables us to quantify >1000 glycosylation variants in body fluids. We show the potential of glycoproteomics for biomarkers, through a case study for early detection of dementia in diabetic patients.

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Short Biography of Presenting Author

I'm a very broadly trained mass spectrometrist, currently working as a Scientist at the Protein Profile Unit at the Weizmann institute. 

I specialise in the most difficult projects in proteomics - mainly glycoproteomics, but also structural proteomics, Top-Down proteomics, protoemics of organisms without genomic databases and other challenges. I use my knowledge in other fields to help biologist adapt and design their projects for success in proteomics and to promote holistic approach to research - integrating consideration of proteomics into the project design.

I've obtained my PhD in Chemical Ecology in the University of Queensland (Australia) and had Post-Doctoral training in Langone NYU Medical Center.