On the issue of infectious etiology of Alzheimer's disease: a literature review

Alzheimer's disease is the most common cause of dementia; however, its etiology remains unclear, and consequently, existing therapies are merely symptomatic. This article analyzes 19 scientific papers from Russian and international sources addressing this issue. The amyloid cascade hypothesis of Alzheimer's disease is the most widely accepted; it is considered in conjunction with the infectious hypothesis, which focuses on the role of infectious agents as a triggering mechanism for the disease. The amyloid cascade hypothesis assigns a central role in the disease's pathogenesis to the accumulation of pathological forms of amyloid-beta (Aβ) in the brain. This process triggers tau protein hyperphosphorylation, neuroinflammation, and neurodegeneration. However, the failure of clinical trials for anti-amyloid drugs has spurred a search for additional triggers, with infectious agents receiving particular attention. According to the modern infectious hypothesis, Aβ functions as an antimicrobial peptide; however, its chronic persistence transforms this protective response into a pathological cascade. This article systematizes scientific perspectives on the common molecular mechanisms underlying the activation of amyloidogenesis by various infectious agents, including NLRP3 inflammasome activation; disruption of autophagy, calcium homeostasis, and blood-brain barrier integrity; and induction of tau protein hyperphosphorylation. Data from the literature regarding specific pathogens associated with Alzheimer's disease are also presented. Herpes simplex virus type 1, Epstein-Barr virus, cytomegalovirus, influenza viruses, SARS-CoV-2, the bacteria Chlamydia pneumoniae, Porphyromonas gingivalis, and Helicobacter pylori, and the protozoan Toxoplasma gondii serve as triggers for the development of Alzheimer's disease.