Alzheimer's disease and infectious agents: a comprehensive review of pathogenic mechanisms and microRNA roles

Abstract

Alzheimer's Disease (AD) is the most prevalent type of dementia and is characterized by the presence of senile plaques and neurofibrillary tangles. There are various theories concerning the causes of AD, but the connection between viral and bacterial infections and their potential role in the pathogenesis of AD has become a fascinating area of research for the field. Various viruses such as Herpes simplex virus 1 (HSV-1), Epstein-Barr virus (EBV), Cytomegalovirus (CMV), influenza viruses, and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), as well as bacteria such as Chlamydia pneumoniae (CP), Helicobacter pylori (HP), Porphyromonas gingivalis (P. gingivalis), Spirochetes and eukaryotic unicellular parasites (e.g., Toxoplasma gondii), have been linked to AD due to their ability to activate the immune system, induce inflammation and increase oxidative stress, thereby leading to cognitive decline and AD. In addition, microRNAs (miRNAs) might play a crucial role in the pathogenesis mechanisms of these pathogens since they are utilized to target various protein-coding genes, allowing for immune evasion, maintaining latency, and suppressing cellular signaling molecules. Also, they can regulate gene expression in human cells. This article provides an overview of the association between AD and various infectious agents, with a focus on the mechanisms by which these pathogens may be related to the pathogenesis of AD. These findings suggest important areas for further research to be explored in future studies.

Keywords: Alzheimer’s disease; bacterial infection; parasite; pathogen; viral infection.

Figure 1

Mechanisms by which SARS-CoV-2 can play role in the pathogenesis of Alzheimer’s Disease (AD). High levels of cytokines and chemokines can cross the blood brain barrier (BBB), causing neuroinflammatory responses and disruption. Virus-infected lymphocytes and monocytes penetrate the central nervous system (CNS), leading to activation of microglia and astrocytes and resulting in neuroinflammation. Activated microglia trigger NADPH oxidase (NOX) enzyme, significantly increasing reactive oxygen species (ROS) production, which impacts neuronal oxidative disruption and can aggravate neurodegenerative diseases, including AD. Also, the virus can enter the nasal epithelium and travel along the olfactory nerve fibers. It uses the ACE2 receptor, present in the nasal epithelium, to enter cells. From there, it hijacks the cellular machinery to replicate and spread along the olfactory nerve. Once the virus reaches the olfactory bulb, it can potentially spread to other parts of the brain. The proximity of the olfactory bulb to the brain allows the virus to access deeper brain structures.