Date of Award
Master of Science in Medical Sciences (MSMS)
Omar M.A EI-Agnaf
Ahmed Al Marzouqi
An abundance of genetic, biochemical and histopathological evidence suggests that the formartion of α-synuclein (α-syn) protein deposits is an important, and likely seminal, step in the development of several important neurodegenerative diseases, the so-called synucleinopathies, including Parkinson’s Disease (PD), intensive research, to date, the only accepted diagnosis for PD is based on clinical criteria. α-syn conversion from soluble monomers into oligomers or fibrils represents a crucial step in synucleinopathies pathogenesis; however, the exact mechanism underlying the cellular aggregation has not been fully elucidated. A growing body of evidence suggests that α-syn soluble oligomers, rather than mature fibrils, are the neurotoxic species. A lack of biomarkers for the early diagnosis of PD is a major obstacle to providing early disease-modifying therapies. Toward this aim, we developed and thoroughly characterized novel confirmation-specific monoclonal antibodies that specifically recognize α-syn pathology. Importantly, our antibodies were able to detect different assemblies of α-syn aggregates, ranging from soluble oligomers to mature insoluble fibrils. Considering the critical pathogenic role of α-syn soluble aggregates, our novel antibodies might provide important diagnostic and therapeutic opportunities.
Next, we developed new immunoassays to quantify different species of α-syn (total α-syn, α-syn oligomers and p-S129- α-syn) levels in cerebrospinal fluid (CSF) from PD patients and age-matched healthy controls. Combining the measurements of different α-syn species in CSF, we found a clear differential CSF pattern between PD and controls. Our results validated the usefulness of combining multiple CSF biomarkers in improving PD diagnostic accuracy and prognostic evaluation.
Majbour, Nour Khaled, "Development and Application of Novel Conformation-Specific Monoclonal Antibodies for Parkinson’s Disease Pathology." (2014). Accounting Dissertations. 18.