Christiane Auray-Blais

Director of the Quebec Provincial Mass Urinary Screening Program. Professor in the Service of Genetics in the Department of Pediatrics at the Faculty of Medicine and Health Sciences at the University of Sherbrooke

Recent advances in biomarker discovery and analysis for lysosomal   storage disorders using mass spectrometry

This presentation will introduce lysosomal storage disorders, and more specifically the characteristics of Fabry disease and mucopolysaccharidoses (MPSs). The detection of novel biomarkers for Fabry disease using a time-of-flight metabolomic approach will be presented along with recent tandem mass spectrometry methods to quantify glycosaminoglycans associated with MPS type I, II and VI.

Roman Zubarev

Director, Proteomics facility, Kalolinska Institute

Label-free proteomics study of Alzheimer’s disease mechanism

Alzheimer’s disease (AD) knows no cure, and its origin is still debated. A plausible hypothesis is that the trigger for the disease is a damaged protein or proteins, but the disease progression may be modulated by the presence or absence of an appropriate phenotype. To test this hypothesis, we developed novel label-free proteomics approaches and investigated blood plasma of 218 individuals in various stages of AD. The main finding is that the healthy controls differ from the individuals with various degrees of dementia by lower levels in blood of proteins damaged by the presence in their sequence of isoaspartic acid (isoAsp). Higher isoAsp levels were found in females than in males, consistent with the prevalence of AD for women. However, no quantitative correlation was found between the isoAsp levels and the AD degree, suggesting that isoAsp in blood could be a risk factor triggering dementia, but not actively participating in its progression. On the other hand, levels of several abundant (‘housekeeping’) proteins could differentiate two early AD stages: stable mild cognitive impairment (MCI) and progressive MCI leading to AD. The total emerging picture supports the hypothesis of dementia is being triggered by an elevated risk factor (e.g. IsoAsp) with subsequent disease progression in the presence of a permissive phenotype characterized by certain levels of housekeeping proteins in blood.