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 (alpha-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/alpha-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 alpha-syn deposits through immune system activation and cross-seeding. In this study, we investigate the humoral response against alpha-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 alpha-syn (alpha-synio(100-114)), curli (Curli(133-141)), PorPhY romonas gingivalis Pg (RgpA(800-812), KPg(328-339)), Aggregatibacter actinomycetemcomitans (UxA1(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 agematched 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.