Antibodies against HSV-1 and Curli Show the Highest Correlation in Parkinson's Disease Patients in Comparison to Healthy Controls.

Parkinson's disease (PD) is a neurodegenerative disorder involving the accumulation of alpha-synuclein (α-syn)/Lewy bodies in the brain and -enteric nervous system. The etiology of the disease is not well understood, but bacterial and viral infections may contribute to the pathogenesis of PD. It has been suggested that the gastrointestinal (GI) complications observed in PD patients may arise from bacterial dysbiosis, leading to curli/α-syn deposits in the enteric nervous system. Enteric bacteria secrete curli, a functional amyloid peptide involved in adhesion to surfaces, cell invasion, and biofilm formation. However, these bacterial amyloids can initiate additional α-syn deposits through immune system activation and cross-seeding. In this study, we investigate the humoral response against α-syn, curli peptides, and various bacterial and viral immunogen peptides in PD patients, and compare them with those in healthy controls (HCs). Polyclonal IgG antibodies (Abs) were detected against peptides derived from α-syn (α-syn 100-114 ), curli (Curli 133-141 ), Porphyromonas gingivalis Pg (RgpA 800-812 , Kpg 328-339 ), Aggregatibacter actinomycetemcomitans (LtxA1 429-445 , LtxA2 64-80 ), Mycobacterium avium subsp. paratuberculosis (MAP3865c 125-133 , MAP1,4-a-gbp 157-173 and MAP_4027 18-32 ), Epstein-Barr virus (EBNA1 400-413 , BOLF1 305-320 ), and Herpes Simplex virus 1 (UI42 22-36 ), as investigated by indirect ELISA of 51 serum samples from PD and 58 sex and age-matched HCs. Significant differences in OD (optical density) values and Abs positivity between PD patients and HCs were observed for Kpg (82.3% vs. 10.3%), followed by RgpA (60.7% vs. 24.1%), curli (51% vs. 22.4%), and UI42 (43.1% vs. 25.8%) in PD, compared to HCs sera ( p < 0.001). No significant difference was found in the ODs obtained from other tested peptides in PD patients, compared to HCs. Significant positive correlations between OD values obtained by ELISA were observed for UI42 and curli ( r = 0.811, p < 0.0001), Kpg and RgpA ( r = 0.659, p < 0.0001), followed by LtxA1 and LtxA2 ( r = 0.653, p < 0.0001). The correlation between the HY scale (Hoehn and Yahr Scale) and LtxA1 ( r = 0.306, p < 0.028) and HY and Kpg ( r = 0.290, p < 0.038) were significantly positive. This study reports a significantly increased humoral response against curli, Pg, and HSV-1 in PD patients, implying that they could be important factors in the pathogenesis of the disease. In addition, the high positive correlation between UI42 and curli may suggest the involvement of HSV-1 in GI dysbiosis. Therefore, the role of each individual pathogen and curli in PD needs to be further investigated.