This review, titled “A review of the roles of pathogens in Alzheimer's disease”, published on August 19, 2024, explores the increasingly recognized role that infections may play in developing and progressing Alzheimer's disease (AD). Although AD has traditionally been attributed to genetic and environmental factors, recent research has focused on the idea that various pathogens may contribute to the disease by disrupting brain homeostasis, promoting neuroinflammation, and interacting with hallmark features of AD, such as amyloid-beta (Aβ) plaques and hyperphosphorylated tau proteins.

The review discusses multiple pathogens, including bacteria, viruses, and fungi, that have been linked to AD. It highlights significant examples such as Herpes Simplex Virus 1 (HSV-1), Chlamydia pneumoniae, and Porphyromonas gingivalis (a key player in chronic periodontal disease). The authors explain how these pathogens may enter the brain through a damaged blood-brain barrier (BBB) or nerve trunk pathways, triggering chronic inflammatory responses and accelerating AD pathology.

One key aspect of the review is the interaction between Aβ and pathogens. Rather than simply being a toxic byproduct, the authors suggest that Aβ may act as an antimicrobial peptide that traps and neutralizes invading pathogens. However, this process could lead to persistent inflammation and plaque formation, contributing to AD progression.

The review addresses pathogen-induced tau hyperphosphorylation, which disrupts neuronal structures, leading to neurodegeneration. Pathogens such as HSV-1 and Helicobacter pylori have been shown to promote tau phosphorylation through various mechanisms, including activating kinases like GSK-3β.