Identification and localization of Chlamydia pneumoniae in the Alzheimer's brain

Abstract

We assessed whether the intracellular bacterium Chlamydia pneumoniae was present in post-mortem brain samples from patients with and without late-onset Alzheimer's disease (AD), since some indirect evidence seems to suggest that infection with the organism might be associated with the disease. Nucleic acids prepared from those samples were screened by polymerase chain reaction (PCR) assay for DNA sequences from the bacterium, and such analyses showed that brain areas with typical AD-related neuropathology were positive for the organism in 17/19 AD patients. Similar analyses of identical brain areas of 18/19 control patients were PCR-negative. Electron- and immunoelectron-microscopic studies of tissues from affected AD brain regions identified chlamydial elementary and reticulate bodies, but similar examinations of non-AD brains were negative for the bacterium. Culture studies of a subset of affected AD brain tissues for C. pneumoniae were strongly positive, while identically performed analyses of non-AD brain tissues were negative. Reverse transcription (RT)-PCR assays using RNA from affected areas of AD brains confirmed that transcripts from two important C. pneumoniae genes were present in those samples but not in controls. Immunohistochemical examination of AD brains, but not those of controls, identified C. pneumoniae within pericytes, microglia, and astroglia. Further immunolabelling studies confirmed the organisms' intracellular presence primarily in areas of neuropathology in the AD brain. Thus, C. pneumoniae is present, viable, and transcriptionally active in areas of neuropathology in the AD brain, possibly suggesting that infection with the organism is a risk factor for late-onset AD.

Chlamydia pneumoniae induces Alzheimer-like amyloid plaques in brains of BALB/c mice

“…Previous study of the relationship of C. pneumoniae and AD revealed genetic material from the organism in olfactory bulbs [16]. In addition, the organism was identified in the entorhinal cortex, the hippocampus, and the temporal cortex of AD brains suggesting that the organism can traffic to these sites [3]. Analogous to the human findings, infection was confirmed in the olfactory bulbs of our experimental mice indicating that the olfactory pathway is vulnerable to infection.…”

“…Recent studies have shown that infection of monocytic cells enhances transmigration across a human brain microvascular endothelial cell layer [25]. Infected perivascular macrophages and monocytes have been observed in and around blood vessels in AD brains [3]. Taken together, these data suggest that infection of leukocytes with C. pneumoniae predisposes the central nervous system (human, and potentially mouse) to infection from the systemic circulation.…”

“…Infection has been implicated as a potential trigger in the initiation of sporadic AD as infectious agents such as Chlamydophila (Chlamydia) pneumoniae, herpes simplex virus-1 (HSV-1), and spirochetes have been associated with AD [3,18,29]. In the initial report linking C. pneumoniae infection with AD, 90% of AD brains were PCR positive for C. pneumoniae, and the organism was detected in regions of the brain that exhibited AD pathology [3].…”

“…In the initial report linking C. pneumoniae infection with AD, 90% of AD brains were PCR positive for C. pneumoniae, and the organism was detected in regions of the brain that exhibited AD pathology [3]. C. pneumoniae was shown to infect microglia, astrocytes, perivascular macrophages, and monocytes [3,26].…”

“…The organisms were metabolically active and could be isolated from the tissue and propagated in cells. Since the initial report identifying C. pneumoniae in the brains of AD patients [3], attempts to replicate this observation have met with mixed results. Several reports were unable to detect C. pneumoniae in archival tissue of AD patients [11,30,32].…”