Constipation is linked to neuroinflammation in early Parkinson’s disease

Background: Constipation is a risk factor for Parkinson’s disease (PD) onset and accelerated progression but the mechanisms underlying this association are unknown. Neuroinflammation in PD has been demonstrated in post-mortem and neuroimaging studies, however, its relationship with constipation has not been investigated. Methods: We used 11C-PK11195 positron emission tomography (PET) to index neuroinflammation in a cohort of 27 people with early-stage PD. The Gastrointestinal Dysfunction Scale for PD (GIDS-PD) was used to assess gut symptom severity. Matched blood and CSF samples were collected. Results: Higher GIDS-PD Constipation scores were associated with 11C-PK11195 binding, in whole brain grey matter, frontal, parietal, temporal and occipital lobes, and multiple subcortical and cortical regions. GIDS-PD Constipation scores were also significantly associated with higher CSF lymphocyte count and blood Th1 cell and Th17-like Th1 cells. Conclusions: Constipation in early PD is associated with widespread neuroinflammation, suggesting a possible mechanism underlying the association between constipation and faster PD progression.