The Infectious Etiology of Alzheimer’s Disease

Abstract

Background: Inflammation is a part of the first line of defense of the body against invasive pathogens, and plays a crucial role in tissue regeneration and repair. A proper inflammatory response ensures the suitable resolution of inflammation and elimination of harmful stimuli, but when the inflammatory reactions are inappropriate it can lead to damage of the surrounding normal cells. The relationship between infections and Alzheimer’s Disease (AD) etiology, especially late-onset AD (LOAD) has been continuously debated over the past three decades.Methods: This review discusses whether infections could be a causative factor that promotes the progression of AD and summarizes recent investigations associating infectious agents and chronic inflammation with AD. Preventive and therapeutic approaches to AD in the context of an infectious etiology of the disease are also discussed.Results: Emerging evidence supports the hypothesis of the role of neurotropic viruses from the Herpesviridae family, especially Human herpesvirus 1 (HHV-1), Cytomegalovirus (CMV), and Human herpesvirus 2 (HHV-2), in AD neuropathology. Recent investigations also indicate the association between Hepatitis C virus (HCV) infection and dementia. Among bacteria special attention is focused on spirochetes family and on periodontal pathogens such as Porphyromonas gingivalis or Treponema denticola that could cause chronic periodontitis and possibly contribute to the clinical onset of AD.Conclusion: Chronic viral, bacterial and fungal infections might be causative factors for the inflammatory pathway in AD.

“Amyloid‐beta accumulation cycle” as a prevention and/or therapy target for Alzheimer's disease

“…In an AD-omics study, HHV-6A and HHV-7 were identified as prominently associated with human AD across three independent cohorts (Readhead et al, 2018). Reports like these support the theory that pathogens trigger AD (Haas & Lathe, 2018;Itzhaki, 2014;Sochocka, Zwolińska, & Leszek, 2017), as well as the role of amyloid-beta as a protection mechanism against viral infection (Li, Liu, Zheng, & Huang, 2018). Although AD cannot be completely explained by the pathogen theory alone, pathogens may act as a risk factor or have an impact on a segment of patients with AD.…”

Oral diseases and inflammatory burden and Alzheimer's disease among subjects aged 75 years or older

“…According to the current understanding of AD's pathology, an inflammation is an important component in the onset and progression of the disease . It has been hypothesized that certain oral diseases could have an influence on AD either by causing a low‐grade inflammation, by activating microglia cells via proinflammatory molecules, or by microbial invasion into the brain . It has also been speculated that the effects of oral diseases on cognitive function might be mediated through changes in diet that in turn are related to impaired mastication …”

Neuroinflammation in mouse models of Alzheimer's disease

“…These conflicting results suggest that NSAIDs do not improve AD pathogenesis directly in the brain, but that systemic inflammation, such as that seen with rheumatoid arthritis, might affect the brain pathologically. Recent evidence also suggests that inflammatory diseases, such as osteoporosis, diabetes, cancer and infection, are possibly implicated in brain disorders, and that these diseases could affect brain function through immune responses elicited in the periphery; that is, through neuroimmune communication. Furthermore, treatment strategies against such diseases might influence brain function and the macroenvironment, as reported for cancer‐related cognitive impairment or HIV‐associated neurocognitive disorder, possibly leading to the onset of brain disorders.…”