Infection and Risk of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is thought to be caused by a combination of genetic and environmental factors. Bacterial or viral infection has been proposed as a potential risk factor, and there is supporting although not entirely consistent epidemiologic and basic science evidence to support its role. Encephalitis caused by influenza has included parkinsonian features. Epidemiological evidence is most compelling for an association between PD and hepatitis C virus. Infection with Helicobacter pylori may be associated not only with PD risk but also response to levodopa. Rapidly evolving knowledge regarding the role of the microbiome also suggests a role of resident bacteria in PD risk. Biological plausibility for the role for infectious agents is supported by the known neurotropic effects of specific viruses, particular vulnerability of the substantia nigra and even the promotion of aggregation of alpha-synuclein. A common feature of implicated viruses appears to be production of high levels of cytokines and chemokines that can cross the blood-brain barrier leading to microglial activation and inflammation and ultimately neuronal cell death. Based on multiple avenues of evidence it appears likely that specific bacterial and particularly viral infections may increase vulnerability to PD. The implications of this for PD prevention requires attention and may be most relevant once preventive treatments for at-risk populations are developed.

Androgens and Parkinson's Disease: A Review of Human Studies and Animal Models

“…Viral infections were proposed as potential risk factors for PD, and there is supporting although not entirely consistent epidemiological and basic science supporting evidence (review Ref. 97 ). In a multihit hypothesis of PD, Sadasivan et al demonstrated that prior exposure of mice to non-neurotropic pandemic influenza A/California/04/2009 H1N1 virus, which triggers brain inflammation, exacerbates their vulnerability to a parkinsonian toxin, MPTP, 1 month later, resulting in heightened loss of DA neurons.…”

Epstein-Barr Virus and Neurological Diseases

“…The main pathological features of PD are degeneration of nigrostriatal dopaminergic neurons, reduction of striatal dopamine, and the formation of abnormal protein aggregates in neurons, such as Lewy vesicles. The aging nervous system is susceptible to the direct and indirect effects of infection, and bacterial or viral infections are considered a potential risk factor ( Pajares et al, 2020 ; Hirsch and Standaert, 2021 ; Smeyne et al, 2021 ). Predominantly lymphocytic leukocytosis, mildly increased protein levels, and EBV antibodies in the CSF and serum of patients with PD suggest the involvement of EBV infection in the development of PD ( Bu et al, 2015 ; Schroder et al, 2018 ).…”

Extragastric Manifestations of Helicobacter Pylori Infection: A Commentary

“…Studies have demonstrated an increased risk of Parkinson's disease in Hp-positive patients, while the eradication of the bacterium doesn't seem to contribute to the reduction of the risk [58]. The overproduction of interleukin 17 (IL-17) and interferon-gamma (INF-Y) release can be related to reduced hippocampal neurogenesis and destruction of the myelin sheath, respectively.…”