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Séminaire impromptu - Brit MollenhauerQuantification of alpha-synuclein in cerebrospinal fluid as Biomarker for Parkinson’s Disease

Abstract :

Séminaire ouvert à tous dans le cadre du DU maladies neurodégénératives,  une invitation de Wassilios Meissner
An university diploma: Neurodegenerative disorders
Special Course : Neurodegenerative disorders, Translational Research : from Physiopathology  to therapeutic approaches Translational research: from pathophysiology to therapeutic approaches

Organizing Committee / Responsables pédagogiques : Pr Bertrand BLOCH ; Pr François TISON


Many fundamental decisions in clinical routine are based on biomarkers, but no widely applicable marker is available for Parkinson’s disease and related disorders with three major problems: (1) our diagnosis based on the UK Brain bank Criteria is too late, when more than 50% of dopaminergic neurons are already degenerated; (2) the diagnosis PD is wrong in 10-20% even when diagnosed by movement disorder experts and (3) upcoming neuropreventive treatments may fail, due to the lack of an objective progression marker.

The presence of total alpha-synuclein in cerebrospinal fluid (CSF) has long been debated, but has been proven in 2008 by mass spectrometry (Mollenhauer et al., 2008). Several assays for the quantification of total alpha-synuclein in CSF showed a decrease in alpha-synuclein-related disorders: Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA) (Tokuda et al., 2006; Mollenhauer et al., 2011; Hong et al., 2010). The decrease could recently also been found in drug-naïve PD cases versus healthy controls (Mollenhauer et al., 2013). And we have shown that CSF alpha-synuclein is derived from neurons of the central nervous system (Mollenhauer et al., 2012).

Between 2009 and 2011 we established a single-center study on 159 at enrolment drug-naïve PD subjects and 110 healthy controls (DeNoPa study), that will be followed biannually for 10-15 years including polysomnography, smell testing, MRI, transcranial ultrasound, CSF, blood sampling, neuropsychological testing and questionnaires on non-motor symptoms. Samples will be used for biomarker validation and to explore new biomarkers by mass-spectrometry including other biological fluids (e.g. urine, saliva).

In parallel we established a new multiplex on an electrochemiluminescence platform (Mesoscale Discovery) to quantify total alpha-synuclein, total tau protein, β-amyloid (1-42) and DJ-1 with a single measurement in a single CSF sample of 50 ul. 

 

© Foto: Polk

Scientific focus :

Biosketch Prof. Dr. Brit Mollenhauer

 Dr. Brit Mollenhauer graduated from Medical School at Georg-August University Goettingen, Germany in 2000. During residency training in Neurology from 2000-2005 in Goettingen, Dr. Mollenhauer was also a member of the National Creutzfeldt-Jakob Disease Surveillance Center under the mentorship of  Prof. Sigrid Poser, where she focused her research activities on the differential diagnoses of prion diseases, with special interest on dementia with Lewy Bodies, Parkinson disease and cerebrospinal fluid biomarker in collaboration with Dres J. Wiltfang and M. Otto. After completing the neurology training in 2005 Dr. Mollenhauer received a research fellowship by the “Stifterverband fuer die Deutsche Wissenschaft” to visit Harvard University and laboratory of Dr. M. Schlossmacher in Boston, USA, where she studied biomarker development and cerebrospinal fluid alpha-synuclein (2005-2007). Since June 2007 she holds a position as Assistant Professor in Neurology at Georg-August University Goettingen, Germany and the Movement Disorder Paracelsus-Elena Klinik, Kassel (Prof. Claudia Trenkwalder). She established her own research team and focuses on human body fluid biomarker detection and assay development for improving diagnosis of movement disorders.

Brit Mollenhauer established a prospective longitudinal cohort of at enrolment 159 de novo PD subjects and 110 matched healthy controls (DeNoPa study) for biomarker studies. She is also member of the executive steering committee of the Parkinson’s Progression Marker Initiative (PPMI) of the Michael J. Fox Foundation.