title: Emerging roles of pathogens in Alzheimer disease.
abstract: Chronic spirochetal infection can cause slowly progressive dementia, cortical atrophy and amyloid deposition in the atrophic form of general paresis. There is a significant association between Alzheimer disease (AD) and various types of spirochete (including the periodontal pathogen Treponemas and Borrelia burgdorferi), and other pathogens such as Chlamydophyla pneumoniae and herpes simplex virus type-1 (HSV-1). Exposure of mammalian neuronal and glial cells and organotypic cultures to spirochetes reproduces the biological and pathological hallmarks of AD. Senile-plaque-like beta amyloid (Aβ) deposits are also observed in mice following inhalation of C. pneumoniae in vivo, and Aβ accumulation and phosphorylation of tau is induced in neurons by HSV-1 in vitro and in vivo. Specific bacterial ligands, and bacterial and viral DNA and RNA all increase the expression of proinflammatory molecules, which activates the innate and adaptive immune systems. Evasion of pathogens from destruction by the host immune reactions leads to persistent infection, chronic inflammation, neuronal destruction and Aβ deposition. Aβ has been shown to be a pore-forming antimicrobial peptide, indicating that Aβ accumulation might be a response to infection. Global attention and action is needed to support this emerging field of research because dementia might be prevented by combined antibiotic, antiviral and anti-inflammatory therapy.
authors.affiliation: International Alzheimer Research Centre, Prevention Alzheimer Foundation, Martigny-Combe, Switzerland. judithmiklossy@bluewin.ch
authors.forename: Judith
authors.initials: J
authors.lastname: Miklossy
mesh_terms: D000544:Alzheimer Disease / Q000382:microbiology*; D000818:Animals; D006801:Humans; D051379:Mice; D013144:Spirochaetales / Q000502:physiology*; D013145:Spirochaetales Infections / Q000382:microbiology*