Biology subjects

van Riesen, C.

Publications and source records attributed to van Riesen, C..

4 recordsLinked to original sources

bioRxiv2025

Detection of alpha synuclein seeding activity in tear fluid in patients with Parkinson's disease

Detection of alpha-synuclein seeding activity in tear fluid (TF) might provide a promising non-invasive biomarker for Parkinsons disease (PD) diagnosis. In this study, we applied the alpha-synuclein seeding amplification assay (aSynSAA) to detect misfolded alpha-synuclein (aSyn) aggregation in TF from PD patients. The discovery cohort included 11 PD patients and 13 controls, and the validation cohort consisted of 9 PD patients and 11 controls without synucleinopathies. The aSynSAA yielded positive results in over 55% of PD patients. These findings were confirmed in a second cohort, including patients with prion diseases as a negative control for synuclein pathology. Our results demonstrate for the first time the ability of aSynSAA to distinguish between PD and control groups in TF, with PD showing the highest seeding activity compared to prion disease and control groups. Further comparisons between cerebrospinal fluid (CSF) and TF samples from the same individuals revealed consistent seeding results across both biofluids. These findings highlight the potential of tear fluid as a novel, accessible medium for detecting Lewy body-specific misfolded synuclein aggregation in PD, which could aid in early diagnosis and disease progression monitoring.

neuroscience↗

bioRxiv2024

Network mechanisms in rapid-onset dystonia-parkinsonism

BackgroundRapid-onset dystonia-parkinsonism (RDP) is a rare neurological disorder caused by mutations in the ATP1A3 gene. Symptoms are characterized by a dystonia-parkinsonism. Recently, experimental studies have shown that the pathophysiology of the disease is based on a combined dysfunction of the cerebellum (CB) and basal ganglia (BG) and that blocking their interaction can alleviate the symptoms. The underlying network mechanisms have not been studied so far. ObjectiveOur aim was to characterize neuronal network activity in the BG and CB and motor cortex in the ouabain model of RDP by site-specific infusion of ouabain. MethodsRats were chronically infused with ouabain either in the CB, striatum (STR) or at both places simultaneously. Motor behavior was scored using published rating systems. Parallel in vivo recordings of local field potentials (LFP) from M1, deep cerebellar nuclei (DCN) and substantia nigra reticulata (SNr) were performed. Data were compared to untreated controls. ResultsOuabain infusion into the cerebellum produced severe dystonia that was associated with increased high-frequency gamma oscillations in the DCNs, which were subsequently transmitted to the BG and M1. Striatal infusion led to parkinsonism and elevated beta- oscillations in SNr that were transmitted to the CB and M1. The simultaneous application of STRs and CB with ouabain resulted in dystonia-parkinsonism and increased beta oscillations in BG, CB, and M1. ConclusionWe demonstrate that symptom-specific beta and gamma oscillations can be transmitted between the BG and CB, which is likely to be very important for the understanding of disease mechanisms.

neuroscience↗

bioRxiv2024

Impaired neurogenesis and synaptogenesis in iPSC-derived Parkinson's patient cortical neurons with D620N VPS35 mutation

Presynaptic dysfunction is an important early process in the pathophysiology of Parkinsons disease (PD) that drives disease progression. To gain insight into the intrinsic synapse impairment in PD, we performed comprehensive electrophysiological and morphological analysis of iPSC-derived cortical neurons derived from PD patients with the VPS35-D620N mutation. Our findings reveal significant impairment in neurogenesis and synaptogenesis within individual patient neurons, culminating to synaptic dysfunction even in the absence of neuronal interactions. The neurons exhibited significantly reduced synaptic responsiveness, fewer synapse and decreased dendritic length and complexity. Thus, the VPS35-D620N mutation in human cortical neurons independently can cause pathophysiology via synaptic dysfunction. Our study highlights the urgent need to develop disease-modifying therapies aimed at preserving synaptic function in PD.

neuroscience↗

bioRxiv2021

Ectosomes and exosomes are distinct proteomic entities that modulate spontaneous activity in neuronal cells

Extracellular vesicles (EVs) are important mediators in intercellular communication. However, understanding the biological origin and functional effects of EVs subtypes has been challenging due to the moderate differences in their physical properties and absence of reliable markers. Here, we characterize the proteomes of ectosomes and exosomes using an improved differential ultracentrifugation protocol and quantitative proteomics. Cytoskeleton and glycolytic proteins are distinctively present in ectosomes, while endosomal sorting complexes proteins and tetraspanins are enriched in exosomes. Furthermore, annexin-A2 was identified as a specific marker for ectosomes derived from cell media and human cerebrospinal fluid. Expression of EGFP as a cytosolic reporter leads to its incorporation in EVs and enables their imaging with higher resolution. Importantly, ectosomes and exosomes internalization in neuronal cells results in the modulation of neuronal spontaneous activity. Our findings suggest that EVs cargoes reflect core intracellular processes, and their functional properties might regulate basic biological and pathological processes.

neuroscience↗