Chlamydophila Pneumoniae and the Etiology of Late-Onset Alzheimer's Disease

Abstract

Sporadic, late-onset Alzheimer's disease (LOAD) is a non-familial, progressive neurodegenerative disease that is now the most common and severe form of dementia in the elderly. That dementia is a direct result of neuronal damage and loss associated with accumulations of abnormal protein deposits in the brain. Great strides have been made in the past 20 years with regard to understanding the pathological entities that arise in the AD brain, both for familial AD (∼5% of all cases) and LOAD (∼95% of all cases). The neuropathology observed includes: neuritic senile plaques (NSPs), neurofibrillary tangles (NFTs), neuropil threads (NPs), and often deposits of cerebrovascular amyloid. Genetic, biochemical, and immunological analyses have provided a relatively detailed knowledge of these entities, but our understanding of the "trigger" events leading to the many cascades resulting in this pathology and neurodegeneration is still quite limited. For this reason, the etiology of AD, in particular LOAD, has remained elusive. However, a number of recent and ongoing studies have implicated infection in the etiology and pathogenesis of LOAD. This review focuses specifically on infection with Chlamydophila (Chlamydia) pneumoniae in LOAD and how this infection may function as a "trigger or initiator" in the pathogenesis of this disease.

Pathogenesis of Chlamydia pneumonia Persistent Illnesses in Autoimmune Diseases

“…Because chlamydial infection engenders a strong inflammatory response, infection by C. pneumoniae, in part, may be responsible for the inflammation observed in the AD affected brain [39]. The results of Balin study demonstrated the frequent infection of microglia and astroglia with C. pneumoniae in the AD-affected brain [7]. Intriguingly, an animal model, in which low-dose infusion of LPS has been used, revealed remarkable parallels with AD inflammation including APP induction, increased cytokine production with microglial reactivity, and temporal lobe pathology [41].…”

“…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 [7,26]. Further immunolabelling studies confirmed the organisms' intracellular presence primarily in areas of neuropathology in the AD brain.…”

“…Although amyloid-beta is considered to be one of the main initiators of these inflammatory processes, some reports suggest that brain infections may also contribute or even initiate the neuroinflammation [39]. Recent data showed the role of C. pneumoniae infection in neuroinflammation and its potential contribution to the pathogenesis of Alzheimer's disease [7].…”

“…Nucleic acids prepared from those samples were screened by polymerase chain reaction (PCR) assay for DNA sequences from the bacterium and showed that brain areas with typical AD-related neuropathology were positive for the organism in 17/19 AD patients [7,26,39]. 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.…”

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“…Accumulation pneumoniae can induce strong inflammatory responses, which could in turn lead to ADrelated neurodegeneration [86].…”