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6.20. MOLCULAR MECHANISMS INVOLVED IN CHRONIC INFECTION IN ALZHEIMER'S DISEASE

Judith Miklossy. Emerging roles of pathogens in Alzheimer disease. Expert Reviews Molecular Médicine. 2011; 2011 ; 13: e30

http://www.expertreviews.org/

Abstract

Chronic spirochetal infection can cause slowly progressive dementia, cortical atrophy and amyloid deposition in the atrophic form of general paresis. There is a statistically significant association between various types of spirochete (including the periodontal pathogens Treponemas and Borrelia burgdorferi),Chlamydophyla pneumoniae and Alzheimer disease (AD). Although there is no significant difference between the frequency of HSV-1 in AD cases and age-matched controls, the number of ApoE4 HSV-1 carriers with AD is reported to be significantly higher compared with disease occurrence in noncarriers. 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 (A, herpes simplex virus type-1 (HSV-1) IgM levelsβ) deposits are also observed in mice following inhalation ofC. pneumoniae 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, and activate 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 indicating that A
attention and action is needed to support this emerging field of research because dementia might bein vivo, and Aβ accumulation and phosphorylation of tau isβ deposition. Aβ has been shown to be a pore-forming antimicrobial peptide,β 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.