Analysis of peripheral blood immune cells from people with Parkinson's disease

A-synuclein pathology is associated to Parkinson’s disease (PD) neurodegeneration, which  affects central and peripheral nervous systems. Accordingly, degenerative signs are observed in the midbrain and putamen, but also in the autonomic system, such as gut and heart denervation. In parallel to the neuronal event and linked to PD progression, adaptive and innate immune changes occur in the brain and periphery. The progression of these pathological events might be related to disease subtypes and might be associated to disease onset and evolution of the prion-like spreading of a-synuclein aggregation. Based on this, the existance of two PD subtypes have been hypothesized: brain-first and body-first. Particularly in the body-first, which is proposed to start in the digestive tube, the vagus nerve is affected very early. This is of relevance since the vagus nerve’s immunomodulatory role will be compromised early in this PD subtype, which might promote inflammation. Thus, we hypothesized a differential immune response in PD subtypes also influenced by sex, that might be of relevance for the disease progression. Here we have performed single-cell transcriptome and Adaptive Immune Receptor Repertoire sequencing analyses of the peripheral blood mononuclear cells from healthy controls (n=10) and PD patients: prodromal (iRBD) (n=10), de novo PD (<4 years from diagnose) brain-first (n=14) & body-first (n=8) and advanced PD (>4 years from diagnose, n=10). Our preliminary bioinformatic data analysis shows a significant change in the adaptive cell compartment.