Evaluation of csgA Prevalence, Gene Expression and Week-to-Week Variability in Participants With Parkinson's Disease and a History of Gastrointestinal Dysfunction

Parkinson's Disease (PD) is a neurodegenerative disorder traditionally associated with motor and non-motor symptoms due to the loss of dopaminergic neurons in the nervous system. Recent research highlights two primary progression patterns: body-first and brain-first PD. In brain-first, PD begins with alpha-synuclein (aSyn) pathology in the brain, particularly in areas like the substantia nigra or olfactory bulb, before potentially involving peripheral systems. Conversely, in the body-first subtype, pathological aSyn aggregates are thought to originate in the enteric nervous system or peripheral autonomic structures, such as the gut and cardiac structures, before spreading to the brain via the vagus nerve. In this subtype of PD, gut dysbiosis and bacterial amyloids could trigger misfolding of aSyn in the enteric nervous system, initiating a cascade of pathology that spreads retrogradely to the brain via the vagus nerve.

The potential influence of the gut microbiome on PD development and progression offers the potential for microbiome targeted therapies to be developed. csgA encodes the major protein subunit of curli, a functional amyloid protein assembly produced by certain gut bacteria like Escherichia coli. Curli proteins help establish extracellular biofilms, and their structural similarity to human amyloids, such as aSyn, suggests they may contribute to pathological processes in PD. CsgA protein could therefore be a potential target for therapies. To develop such interventions, understanding the prevalence and variability of csgA within the microbiomes of individual patients is critical because this information will help guide the development of assays to assess pharmacodynamic effects of a potential therapy. This study therefore focuses on studying the prevalence and inter-individual and week-to-week variability of csgA in the PD population.