Multi-pathogen infections and Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a chronic neurodegenerative disease associated with the overproduction and accumulation of amyloid-β peptide and hyperphosphorylation of tau proteins in the brain. Despite extensive research on the amyloid-based mechanism of AD pathogenesis, the underlying cause of AD is not fully understood. No disease-modifying therapies currently exist, and numerous clinical trials have failed to demonstrate any benefits. The recent discovery that the amyloid-β peptide has antimicrobial activities supports the possibility of an infectious aetiology of AD and suggests that amyloid-β plaque formation might be induced by infection. AD patients have a weakened blood–brain barrier and immune system and are thus at elevated risk of microbial infections. Such infections can cause chronic neuroinflammation, production of the antimicrobial amyloid-β peptide, and neurodegeneration. Various pathogens, including viruses, bacteria, fungi, and parasites have been associated with AD. Most research in this area has focused on individual pathogens, with herpesviruses and periodontal bacteria being most frequently implicated. The purpose of this review is to highlight the potential role of multi-pathogen infections in AD. Recognition of the potential coexistence of multiple pathogens and biofilms in AD’s aetiology may stimulate the development of novel approaches to its diagnosis and treatment. Multiple diagnostic tests could be applied simultaneously to detect major pathogens, followed by anti-microbial treatment using antiviral, antibacterial, antifungal, and anti-biofilm agents.

The Hippocampal Vulnerability to Herpes Simplex Virus Type I Infection: Relevance to Alzheimer’s Disease and Memory Impairment

“…All in all, persistent HSV-1 infection and reactivation may present as risk factors, which likely interacts with and adds to other risk factors (e.g., age, ApoE4 genotype and other microbial infections) in the development of AD and other hippocampalrelated brain disorders, as reviewed in Wainberg et al (2021) and Vigasova et al (2021). However, there is no evidence of causation in humans yet as HSV-1 reactivation cannot be measured in the living brain, as Mancuso et al (2019) suggested.…”

Viruses, periodontitis, and comorbidities

“…Alzheimer disease is a chronic neurodegenerative disease associated with the overproduction and accumulation of amyloid‐β peptide and hyperphosphorylation of tau proteins in the brain. Despite extensive research on the amyloid‐based mechanism of Alzheimer disease pathogenesis, its underlying cause is not fully understood 138 . Alzheimer disease patients exhibit neuroinflammation consistent with infection, including microglial activation, inflammasome activation, complement activation, and altered cytokine profiles.…”

Inflammation in Focus: The Beginning and the End

“…Nowadays it is more and more accepted that chronic inflammation provides the base of serious chronic, noninflammatory diseases including cardiovascular, neurodegenerative and bowel diseases, diabetes, arthritis, fibrosis and cancer. In the aetiology of the Alzheimer's disease scientists found links between various pathogens and the development of the disease [51][52][53]. There are data indicating that in lateral sclerosis and in multiple sclerosis bacterial or viral infection can be one of the factors that initiates the disease.…”