Glycan-based biomarkers for the diagnostics of Alzheimer´s disease

• Applicants: Professorin Dr. Véronique Blanchard, Ph.D.; Privatdozent Dr. Oliver Peters
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Biochemistry ; Molecular Biology and Physiology of Neurons and Glial Cells ; Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2018 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 413741487

Alzheimer´s disease (AD) is the most common neurodegenerative disorder affecting the elderly and its prevalence is expected to increase massively in the future. The relatively certain diagnosis of AD is based on a combination of imaging, psychological testing and CSF biomarkers. The definitive diagnosis of AD can only be carried out post-mortem by pathologic examination. Novel CSF and/or blood biomarkers are needed to improve early and differential diagnosis of AD and to follow patients longitudinally as well as in the course of clinical trials. The applicants have recently developed a platform to analyze the glycome from serum, plasma and CSF. This study aims at the discovery of novel glycan biomarkers of AD by analyzing the N- and O-glycome both plasma and CSF from a collective of AD patients (n=100), patients suffering from another form of dementia (n=100) and healthy controls (n=100). Moreover, it is expected that analysis of the N- and O-glycome of plasma and CSF will add to the understanding of the pathogenesis causes of this proteopathy. Data obtained by MALDI-TOF mass spectrometry will be combined as a glycan score then compared with the existing CSF biomarkers and psychological tests performed in the clinic of neurology. Finally, glycoproteins that are responsible for modified glycosylation will be identified by LC-MS after lectin enrichment of a restricted number of CSF samples (n=20 per group). The results of the project will be the basis of future studies, addressing the use of AD-associated glycan disorders for the development of new diagnostic assays, as well as the possible role of N- and O-glycans in the pathogenesis of the disease.

• DFG Programme: Research Grants