Biology subjects

Engen, P. A.

Publications and source records attributed to Engen, P. A..

2 recordsLinked to original sources

bioRxiv2026

Seed Amplification Assay-Based Detection of Alpha-Synuclein Aggregates Outperforms Immunohistochemical Analysis in the Intestinal Mucosal Biopsies of Parkinson's Disease and Multiple System Atrophy Participants

Objective: To determine whether an -synuclein (-Syn) seed amplification assay (SAA) detects seeding-competent aggregates in endoscopic mucosal biopsies, differs by gastrointestinal region, registers pathology more frequently than immunohistochemistry (IHC), and associates with Parkinson disease (PD) diagnosis, disease duration or severity. Design: This cross-sectional, proof-of-concept diagnostic accuracy study analyzed duodenum, ileum, and sigmoid biopsies from PD participants, age- and sex-matched healthy controls (HC), plus exploratory multiple system atrophy (MSA) subtypes [parkinsonian (MSA-P) and cerebellar (MSA-C)]. Ileal and sigmoid PD and HC biopsies were assessed using proteinase K-resistant phospho-Ser129 IHC. SAA positivity was evaluated against clinical and biological measures. Results: In PD, SAA detected seeding competent -Syn aggregates with high observed specificity (97.5-100%) and region-dependent sensitivity (18/37, 48.65% in ileum and 36/56, 64.29% in sigmoid). Sigmoid SAA positivity increased significantly with PD disease duration (40.00% at <5 years, 73.33% at 5-10 years, and 93.75% at >10 years), independent of motor severity, whereas ileal positivity remained stable across disease stages. In 37 paired sigmoid biopsies, SAA detected -Syn aggregates 2.8-fold more frequently than IHC. Sigmoid seeding activity was detected in all five MSA-P, but not in two MSA-C. IHC did not detect aggregates in any MSA. Conclusions: In PD, -Syn SAA detected seeding-competent -Syn aggregates in endoscopic mucosal biopsies with high observed specificity, moderate sensitivity, and approximately 2.8-fold higher detection rate than IHC in sigmoid. Positive SAA in MSA patients supports GI involvement across synucleinopathies. SAA detection in PD differed by intestinal region and disease duration, supporting further validation of intestinal SAA as a PD biomarker.

neuroscience↗

bioRxiv2022

Integrated multi-cohort analysis of the Parkinson's disease gut metagenome

BackgroundThe gut microbiome is altered in several neurologic disorders including Parkinsons disease (PD). ObjectivesProfile the fecal gut metagenome in PD for alterations in microbial composition, taxon abundance, metabolic pathways, and microbial gene products, and their relationship with disease progression. MethodsShotgun metagenomic sequencing was conducted on 244 stool donors from two independent cohorts in the United States, including individuals with PD (n=48, n=47, respectively), environmental Household Controls (HC, n=29, n=30), and community Population Controls (PC, n=41, n=49). Microbial features consistently altered in PD compared to HC and PC subjects were identified. Data were cross-referenced to public metagenomic datasets from two previous studies in Germany and China to determine generalizable microbiome features. ResultsThe gut microbiome in PD shows significant alterations in community composition. Robust taxonomic alterations include depletion of putative "beneficial" gut commensals Faecalibacterium prausnitzii and Eubacterium and Roseburia species, and increased abundance of Akkermansia muciniphila and Bifidobacterium species. Pathway enrichment analysis and metabolic potential, constructed from microbial gene abundance, revealed disruptions in microbial carbohydrate and lipid metabolism and increased amino acid and nucleotide metabolism. These global gene-level signatures indicate an increased response to oxidative stress, decreased cellular growth and microbial motility, and disrupted inter-community signaling. ConclusionsA metagenomic meta-analysis of PD shows consistent and novel alterations in taxonomic representation, functional metabolic potential, and microbial gene abundance across four independent studies from three continents. These data reveal stereotypic changes in the gut microbiome are a consistent feature of PD, highlighting potential diagnostic and therapeutic avenues for future research.

microbiology↗