Infections contribute to proteinopathies in neurodegenerative diseases and in some post‐viral persistent symptoms

Abstract

AbstractBackgroundThe failure of therapies directed against amyloid‐beta makes us reconsider the theory of the amyloid cascade in Alzheimer’s disease (AD). Infections are suspected to contribute to the disease process. Co‐infection with herpes simplex virus type 1 (HSV‐1) and cytomegalovirus (CMV) results in a higher odds ratio than an individual heterozygous for APOE 4 to develop AD. The objective is to propose a simplified biological model considering the scientific literature to explain the contribution of infections to proteinopathies resulting in neurodegenerative disease for possible integration into a predictive model.MethodWe performed a narrative review of the literature on the cellular mechanisms affected by HSV‐1, CMV and AD.ResultWe propose an hypothetical model supporting that infections can contribute significantly to the different pathophysiological processes of AD via an increase in the failure of misfolding required to obtain a functional conformation of proteins and a decrease in the clearance of proteins with a potentially toxic conformation. Some important changes also involve immunosenescence, as well as compromise of neurogenesis. Immunosenescence allows latent infections, such as HSV‐1 and CMV, to reactivate, spread, and cause cellular changes favorable to AD development.ConclusionThe model explains the cellular changes observed in AD. Given that effective treatments already exist for many of the infections, additional studies are urgently needed to detail the specific contribution of each infection.