A5008858542- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Genetic Neurodegenerative Diseases
- Olfactory and Sensory Function Studies
- Neurological diseases and metabolism
- Biochemical Analysis and Sensing Techniques
- Botulinum Toxin and Related Neurological Disorders
- Congenital heart defects research
- Autism Spectrum Disorder Research
- Nuclear Receptors and Signaling
- RNA regulation and disease
- RNA and protein synthesis mechanisms
- Autophagy in Disease and Therapy
- Spinal Dysraphism and Malformations
- Protease and Inhibitor Mechanisms
- Allergic Rhinitis and Sensitization
- Advanced Chemical Sensor Technologies
- Neurological and metabolic disorders
- Genomic variations and chromosomal abnormalities
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Renal and related cancers
- Ion channel regulation and function
- Neurogenetic and Muscular Disorders Research
University of Göttingen
2022-2025
Paracelsus Elena Klinik Kassel
2021-2025
Nephrologisches Zentrum Goettingen
2025
Universitätsmedizin Göttingen
2024
Helmholtz Zentrum München
2016-2021
Technical University of Munich
2020
Zentrum für Kinderheilkunde
2011
Essen University Hospital
2011
Misfolded α-synuclein (αSyn) aggregates (αSyn-seeds) in cerebrospinal fluid (CSF) are biomarkers for synucleinopathies such as Parkinson's disease (PD). αSyn-seeds have been detected prodromal cases with isolated rapid eye movement sleep behavior disorder (iRBD).
Abstract Parkinson’s disease is increasingly prevalent. It progresses from the pre-motor stage (characterised by non-motor symptoms like REM sleep behaviour disorder), to disabling motor stage. We need objective biomarkers for early/pre-motor stages be able intervene and slow underlying neurodegenerative process. Here, we validate a targeted multiplexed mass spectrometry assay blood samples recently diagnosed patients ( n = 99), individuals with isolated disorder (two cohorts: 18 54...
ABSTRACT Background Dystonia is clinically and genetically heterogeneous. Despite being a first‐line testing tool for heterogeneous inherited disorders, whole‐exome sequencing has not yet been evaluated in dystonia diagnostics. We set up pilot study to address the yield of early‐onset generalized dystonia, disease subtype enriched monogenic causation. Methods Clinical coupled with bioinformatics analysis detailed phenotyping mutation carriers was performed on 16 consecutive cases undefined...
Up to 40% of neurodevelopmental disorders (NDDs) such as intellectual disability, developmental delay, autism spectrum disorder, and motor abnormalities have a documented underlying monogenic defect, primarily due de novo variants. Still, the overall burden variants well novel disease genes in NDDs await discovery. We performed parent-offspring trio exome sequencing 231 individuals with NDDs. Phenotypes were compiled using human phenotype ontology terms. The diagnostic yield was 49.8% (n =...
ABSTRACT Background Recent studies point toward a significant impact of cardiovascular processes and inflammation on Parkinson's disease (PD) progression. Objective The aim this study was to assess established markers neuronal function, inflammation, risk by high‐throughput sandwich immune multiplex panels in deeply phenotyped PD. Methods Proximity Extension Assay technology 273 applied plasma 109 drug‐naive at baseline (BL) patients with PD (BL, 2‐, 4‐, 6‐year follow‐up [FU]) 96 healthy...
Dystonia is a prevalent, heterogeneous movement disorder characterized by involuntarily abnormal postures. Biomarkers of dystonia are notoriously lacking. Here, biomarker reported for histone lysine methyltransferase (KMT2B)-deficient dystonia, leading subtype among the individually rare monogenic dystonias. It was derived applying support vector machine to an episignature 113 DNA CpG sites, which, in blood cells, showed significant epigenome-wide association with KMT2B deficiency and at...
Abstract Lysosomal and synaptic dysfunctions are hallmarks in neurodegeneration potentially relevant as biomarkers, but data on early Parkinson’s disease (PD) is lacking. We performed targeted mass spectrometry with an established protein panel, assessing autophagy function cerebrospinal fluid (CSF) of drug-naïve de novo PD, sex-/age-matched healthy controls (HC) cross-sectionally (88 46 HC) longitudinally (104 58 over 10 years. Multiple markers autophagy, plasticity, secretory pathways were...
Mutations and multiplications in the SNCA gene , encoding alpha-synuclein (aSyn), are associated with familial forms of Parkinson's disease (PD). We report identification a novel missense mutation (NM_000345.4, cDNA 174G>C; protein K58N) PD patient using whole exome sequencing, describe comprehensive molecular cellular analysss effects this mutation. The exhibited typical sporadic early onset benign course. Biophysical studies revealed that K58N substitution causes local structural effects,...
Diagnosing α-synucleinopathies and assessing target engagement in trials is hindered by the lack of reliable biomarkers. Here, we introduce a first-in-kind quantitative, highly sensitive, disease-specific diagnostic assay, named Seeding Amplification ImmunoAssay (SAIA), developed validated to detect synucleinopathy-linked disorders. To this end, used wide range specimens, including 37 brain homogenates (BH) 559 cerebrospinal fluid (CSF) samples from subjects with diverse synucleinopathy...
Abstract Background The pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) and its association with neurodegenerative disorders is poorly understood. Objectives aim was to determine the prevalence α‐synuclein pathology in iNPH associations clinical characteristics. Methods We used seed amplification assay (synSAA) retrospectively analyze cerebrospinal fluid (CSF) from a large single‐center cohort (n = 144). Clinical assessments comprised Unified Parkinson's Disease Rating...
Abstract Misfolding and aggregation of alpha-synuclein (αSyn) play a key role in the pathophysiology Parkinson’s disease (PD). Despite considerable advances diagnostics, an early differential diagnosis PD still represents major challenge. We innovated immuno-infrared sensor (iRS) platform for measuring αSyn misfolding. analyzed cerebrospinal fluid (CSF) from two cohorts comprising cases, atypical Parkinsonian disorders, controls. obtained AUC 0.90 ( n = 134, 95% CI 0.85–0.96) separating...
Background The genetic architecture of non-acquired focal epilepsies (NAFEs) becomes increasingly unravelled using genome-wide sequencing datasets. However, it remains to be determined how this emerging knowledge can translated into a diagnostic setting. To bridge gap, we assessed the outcomes exome (ES) in NAFE. Methods 112 deeply phenotyped patients with NAFE were included study. Diagnostic ES was performed, followed by screen detect variants uncertain significance (VUSs) 15...
Calcium/calmodulin-dependent protein kinases (CaMKs) are key mediators of calcium signaling and underpin neuronal health. Although widely studied, the contribution CaMKs to Mendelian disease is rather enigmatic. Here, we describe an unusual neurodevelopmental phenotype, characterized by milestone delay, intellectual disability, autism, ataxia, mixed hyperkinetic movement disorder including severe generalized dystonia, in a proband who remained etiologically undiagnosed despite exhaustive...
The MDS-Unified Parkinson's disease (PD) Rating Scale (MDS-UPDRS) is the most used scale in clinical trials. Little known about predictive potential of its single items.To systematically dissect MDS-UPDRS to predict PD progression.574 de novo patients and 305 healthy controls were investigated at baseline (BL) single-center DeNoPa (6-year follow-up) multi-center PPMI (8-year cohorts. We calculated cumulative link mixed models items for odds ratios (OR) class change within scale. Models...
ABSTRACT Background Reduced olfaction is a common feature of patients with typical Parkinson disease (PD). We sought to develop and validate simplified smell test as screening tool help identify PD explore its differentiation from other forms parkinsonism. Methods used the Sniffin’ Sticks Identification Test (SST-ID) University Pennsylvania Smell (UPSIT), together data three case-control studies, compare in 301 or dementia Lewy bodies (DLB) 36 subjects multiple system atrophy (MSA), 32...
ABSTRACT Impaired olfaction can be associated with neurodegenerative disorders. We examined odor identification in newly diagnosed patients parkinsonism and those at increased risk, measured olfactory performances longitudinally, juxtaposed results to cerebrospinal fluid (CSF) values. Using Sniffin’-Sticks-Identification Tests (SST-ID), we 312 age-matched individuals a German center, including: 126 Parkinson disease (PD), 109 healthy controls, 25 other disorders 52 REM-sleep behavior...