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

Abstract

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-syn100–114), curli (Curli133–141), Porphyromonas gingivalis Pg (RgpA800–812, Kpg328–339), Aggregatibacter actinomycetemcomitans (LtxA1429–445, LtxA264–80), Mycobacterium avium subsp. paratuberculosis (MAP3865c125–133, MAP1,4-a-gbp157–173 and MAP_402718–32), Epstein–Barr virus (EBNA1400–413, BOLF1305–320), and Herpes Simplex virus 1 (UI4222–36), 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.

Glucose-6-Phosphatase-Dehydrogenase activity as modulative association between Parkinson’s disease and periodontitis

“…P-values for the presence of Porphyromonas gingivalis were statistically significant in all PK biospecimens (serum, saliva, and RNA; −0.141, −0.141, and −0.103, respectively). This may indicate a special role for this known keystone pathogen, LPS, and gingipains in amplifying systemic inflammation for PK pathogenesis (Adams et al, 2019;Olsen et al, 2020;Jasemi et al, 2022;Lyra et al, 2022). NHANES data have shown that periodontitis is associated with leukocytosis in PK patients (Botelho et al, 2020) underlining an inflammatory context as a well-accepted part of the pathology (Hirsch et al, 2005;Lee et al, 2009).…”

Disease- and stage-specific alterations of the oral and fecal microbiota in Alzheimer's disease

“…The Curli type amyloid protein, which is found in the outer membranes of several Enterobacteriaceae is an important factor for biofilm formation ( 83 ). It shows similarities to human Aβ and α-synuclein which is implicated in Parkinson's disease and may contribute to pathology through immune activation via systemic or vagal pathways ( 84 ). So far, animal experiments showed a higher abundance of Curli in AD and Parkinson's disease mouse models ( 85 , 86 ); however, substantiation of these patterns in humans is still lacking behind, particularly for AD.…”