Biology subjects

Scheperjans, F.

Publications and source records attributed to Scheperjans, F..

4 recordsLinked to original sources

bioRxiv2026

Stools and stool-derived extracellular vesicles from patients with Parkinson`s disease show alpha-4 synuclein seeding activity

BackgroundParkinsons disease (PD) is a neurodegenerative disorder for which there is currently no cure or reliable biomarker for early detection or for evaluating the effectiveness of potential treatments. PD pathology is driven by misfolding and subsequent accumulation of alpha-synuclein (Syn) protein into pathological aggregates within neurons and glial cells. Seed amplification assay (SAA) is a highly sensitive and specific diagnostic tool developed to detect pathological Syn species in the cerebrospinal fluid (CSF) of PD patients. However, Syn aggregates are present in multiple tissues and biosamples, including stools. In this study, we aimed to investigate the potential diagnostic value of SAA using stool samples from PD patients and healthy controls (HC). MethodsStool samples from PD patients (n=45) and healthy controls (n=35) were analysed for the presence of Syn species using slot blot assays with a panel of six Syn antibodies, and ELISA assays. Samples were subjected to SAA, and the end-point products (SAA EP) were characterised using transmission electron microscopy (TEM). Extracellular vesicles (EVs) were isolated from the subset of samples (n=5 per group) using size exclusion chromatography and characterized by TEM. The seeding activity of isolated EVs was evaluated using SAA, followed by TEM analysis of SAA EP. ResultsProtein extracts from both PD and HC stool samples revealed pathological Syn species in the slot blot assay using the phosphorylated Syn antibody, pS129 and conformation-specific antibodies, MJFR-14 and 5G4. ELISA showed significantly elevated total Syn levels in PD samples compared to HC, although no differences in aggregated Syn levels were detected. In stool protein extracts, SAA demonstrated 55.6% sensitivity and 60% specificity. When applied to stool-derived EVs from PD patients and controls, sensitivity increased to 100%, while specificity remained at 60%. Notably, SAA applied to stool-derived EVs pre-incubated with recombinant monomeric Syn achieved 100% sensitivity and 100% specificity. ConclusionThese findings suggest that SAA applied to EVs isolated from stool samples, particularly after pre-incubation with recombinant monomeric Syn, may serve as a valuable, non-invasive screening tool for the diagnosis of PD.

neuroscience↗

bioRxiv2023

Comparison of phage and plasmid populations present in the gut microbiota of Parkinson's disease patients

The aging population worldwide is on the rise, leading to a higher number of Parkinsons disease (PD) cases each year. PD is presently the second most prevalent neurodegenerative disease, affecting an estimated 7-10 million individuals globally. This research aimed to identify mobile genetic elements in human fecal samples using a shotgun metagenomics approach. We found over 44,000 plasmid contigs and compared plasmid populations between PD patients (n = 68) and healthy controls (n = 68). Significant associations emerged between Body Mass Index (BMI) and plasmid alpha diversity. Moreover, the gene populations present on plasmids displayed marked differences in alpha and beta diversity between PD patients and healthy controls. We identified a considerable number of phage contigs that were differentially abundant in the two groups. Moreover, we improved the continuity and identification of the protein coding regions of the phage contigs by implementing alternative genetic codes. We built a classification system based on a selection of the phages differentially abundant in the groups. A machine learning approach based on phage abundances allowed a classification of the subjects into the PD or control group with an area under curve (AUC) of 0.969.

microbiology↗

bioRxiv2023

Metagenome-assembled microbial genomes from Parkinson's disease fecal samples

The human gut microbiome composition has been linked to Parkinsons disease (PD). However, knowledge of the gut microbiota on the genome level is still limited. Here we performed deep metagenomic sequencing and binning to build metagenome-assembled genomes (MAG) from 136 human fecal microbiomes (68 PD samples and 68 control samples). We constructed 952 non-redundant high-quality MAGs and compared them between PD and control groups. Among these MAGs, there were 22 different versions of Collinsella and Prevotella MAGs, indicating high variability of those genera in the human gut environment. Microdiversity analysis indicated that Ruminococcus bromii was statistically significantly (p < 0.002) more diverse on the strain level in the control samples compared to the PD samples. In addition, by clustering all genes and performing presence-absence analysis between groups, we identified several control-specific (p < 0.05) related genes, such as speF and Fe-S oxidoreductase. We also report detailed annotation of MAGs, including Clusters of Orthologous Genes (COG), Cas operon type, antiviral gene, prophage, and secondary metabolites biosynthetic gene clusters, which can be useful for providing a reference for future studies.

genomics↗

bioRxiv2019

Gut microbiome signatures of risk and prodromal markers of Parkinson's disease

ObjectivesAlterations of the gut microbiome in Parkinsons disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they may be related to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition. MethodsEstablished risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function and medication were studied in relation to bacterial -/{beta}-diversity, enterotypes, and taxonomic composition in stool samples of 666 elderly TREND study participants. ResultsAmong risk and prodromal markers, physical inactivity, constipation and age showed associations with - and {beta}-diversity, and for both measures subthreshold parkinsonism and physical inactivity showed interaction effects. Moreover, male sex, possible REM-sleep behavior disorder (RBD), smoking as well as body-mass-index, antidiabetic and urate-lowering medication were associated with {beta}-diversity. Physical inactivity and constipation severity were increased in individuals with the Firmicutes-enriched enterotype. Subthreshold parkinsonism was least frequently observed in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical inactivity, possible RBD, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history and the overall prodromal PD probability showed no significant microbiome associations. InterpretationSeveral risk and prodromal markers of PD are associated with changes in gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases.

neuroscience↗