The Development of Premortal Diagnostic Test for a-Synucleinopathies in Cerebrospinal Fluid and Blood

von Sezgi Canaslan Eyyuboglu
Dissertation
Datum der mündl. Prüfung:2024-01-17
Erschienen:2024-01-26
Betreuer:Prof. Dr. Inga Zerr
Gutachter:Prof. Dr. Tiago Fleming Outeiro
Gutachter:Prof. Dr. Alexander Flügel
Gutachter:Prof. Dr. Michael Werner Sereda
Gutachter:Prof. Dr. Christine Stadelmann-Nessler
Gutachter:Prof. Dr. André Fischer
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-10317

 

 

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Zusammenfassung

Englisch

Synucleinopathies represent a group of neurodegenerative disorders characterized by the accumulation of abnormal α-synuclein protein aggregates in the central nervous system. Accurate and early diagnosis is crucial for effective treatment and management. This thesis explores the potential of various biomarkers in synucleinopathies, shedding light on their diagnostic accuracy, and clinical relevance. The study involves the analysis of CSF and blood biomarkers from synucleinopathy patients and control groups. A range of biomarkers including neurofilament light (NfL), prion proteins (PrPC and shedPrP), ubiquitin C-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), Tau proteins (t-Tau and pTau181) and αsynuclein was investigated using assays based on the ultra-sensitive SIMOA technology and evaluated in terms of diagnostic accuracy. Neurofilament light emerges as a promising marker, while prion proteins exhibit distinct patterns in synucleinopathies. Furthermore, the study explores the complexities within synucleinopathies, including the intricate interplay between biomarkers and clinical measures and the nuanced differentiations among subgroups. Key findings include significant regulation of PrPC and shedPrP in synucleinopathies in comparison to controls suggesting their potential as sensitive diagnostic tools. Additionally, investigating the stability of biomarkers under different conditions and exploring their role in disease mechanisms may offer new insights into the pathophysiology of synucleinopathies. Aggregated α-synuclein was also detected using a real-time quaking-induced conversion assay, called RTQuIC. According to the signal response of RT-QuIC, we could discriminate synucleinopathies from controls. In conclusion, this thesis contributes to the evolving field of synucleinopathy research by elucidating the potential of biomarkers and emphasizing the need for comprehensive investigations to fully harness their diagnostic and therapeutic capabilities.
Keywords: alpha-synuclein; synucelinopathies; RT-QuIC; SIMOA; Biomarker; Parkinson's Disease
Schlagwörter: alpha-synuclein; synucleinopathies; RT-QuIC; SIMOA; Biomarker; Parkinson's Disease