title: Immunohistological detection of Chlamydia pneumoniae in the Alzheimer's disease brain.
abstract: BACKGROUND
  Sporadic late-onset Alzheimer's disease (AD) appears to evolve from an interplay between genetic and environmental factors. One environmental factor that continues to be of great interest is that of Chlamydia pneumoniae infection and its association with late-onset disease. Detection of this organism in clinical and autopsy samples has proved challenging using a variety of molecular and histological techniques. Our current investigation utilized immunohistochemistry with a battery of commercially available anti-C. pneumoniae antibodies to determine whether C. pneumoniae was present in areas typically associated with AD neuropathology from 5 AD and 5 non-AD control brains.
  
  
  RESULTS
  Immunoreactivity for C. pneumoniae antigens was observed both intracellularly in neurons, neuroglia, endothelial cells, and peri-endothelial cells, and extracellularly in the frontal and temporal cortices of the AD brain with multiple C. pneumoniae-specific antibodies. This immunoreactivity was seen in regions of amyloid deposition as revealed by immunolabeling with two different anti-beta amyloid antibodies. Thioflavin S staining, overlaid with C. pneumoniae immunolabeling, demonstrated no direct co-localization of the organism and amyloid plaques. Further, the specificity of C. pneumoniae labeling of AD brain sections was demonstrated using C. pneumoniae antibodies pre-absorbed against amyloid β 1-40 and 1-42 peptides.
  
  
  CONCLUSIONS
  Anti-C. pneumoniae antibodies, obtained commercially, identified both typical intracellular and atypical extracellular C. pneumoniae antigens in frontal and temporal cortices of the AD brain. C. pneumoniae, amyloid deposits, and neurofibrillary tangles were present in the same regions of the brain in apposition to one another. Although additional studies are required to conclusively characterize the nature of Chlamydial immunoreactivity in the AD brain, these results further implicate C. pneumoniae infection with the pathogenesis of Alzheimer's disease.
authors.affiliation: Pathology/Microbiology/Immunology and Forensic Medicine Department, Philadelphia College of Osteopathic Medicine, 4170 City Ave, Philadelphia, Pennsylvania, USA. BrianBa@pcom.edu
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Hammond
authors.forename: Loretta R
authors.initials: LR
authors.lastname: Hallock
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Howanski
authors.forename: Denah M
authors.initials: DM
authors.lastname: Appelt
authors.forename: C Scott
authors.initials: CS
authors.lastname: Little
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Balin
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000276:immunology* / Q000382:microbiology*; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism; D052160:Benzothiazoles; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000502:physiology; D002540:Cerebral Cortex / Q000276:immunology / Q000382:microbiology; D002690:Chlamydia Infections / Q000276:immunology* / Q000382:microbiology*; D016993:Chlamydophila pneumoniae; D004396:Coloring Agents; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology; D015203:Reproducibility of Results; D013844:Thiazoles; D014015:Tissue Banks
chemical_list: D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D004396:Coloring Agents; D013844:Thiazoles; C009462:thioflavin T