Chlamydophila (Chlamydia) pneumoniaein the Alzheimer's brain

Abstract

We assessed the presence and characteristics of the intracellular pathogen Chlamydophila (Chlamydia) pneumoniae in brain-tissue samples from 25 patients with late-onset Alzheimer's disease (AD) and 27 non-AD control individuals. 20/ 27 AD patients, but only 3/27 controls, were PCR-positive in multiple assays targetting the Cpn1046 and Cpn0695 genes. Culture of the organism from braintissue homogenate from one AD patient, and assessment of various chlamydial transcripts in RNA preparations from several patients, demonstrated that the organisms were viable and metabolically active in those samples. Immunohistochemical analyses showed that astrocytes, microglia, and neurons all served as host cells for C. pneumoniae in the AD brain, and that infected cells were found in close proximity to both neuritic senile plaques and neurofibrillary tangles in the AD brain. These observations confirm and significantly extend our earlier study suggesting that this unusual pathogen may play a role in the neuropathogenesis characteristic of AD.

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“…In this respect, there is evidence suggesting that some relationship exists between the APOE4 gene product and the pathobiology of the intracellular Chlamydophila (Chlamydia) pneumoniae involved in AD pathogenesis [8,9]. Moreover, the risk of developing AD is much greater in patients HSV-1-positive in brain who also possess an APOE4 allele than in those with only one of these factors [29].…”

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“…Positive association Wndings obtained in brain tissues from patients with AD and controls are strengthened by the fact that the investigators were blinded for the disease status at least in some studies which showed association between AD and Cpn, rendering false positive results e.g. by contamination or observer bias unlikely [20,22]. However, the signiWcance of these Wndings is tempered by the fact that the tissue samples were not additionally analyzed by independent laboratories and could not be reconWrmed in other studies.…”

“…In another study, they reported that by amplifying two diVerent chlamydial target genes Cpn0695 and Cpn1046, 20 out of 25 (80%) samples of patients with AD compared to 3 out of 27 (11.1%) samples of the control group were Cpn-DNA positive [22]. Using immunohistochemical staining, they observed a co-localization of Cpn with amyloid plaques and NFTs, two of the major pathophysiological correlates of AD [22].…”

“…However, it must be noted that the results arguing for a pathogenic role of C. pneumoniae infection in AD have been obtained in only one group [20][21][22][23], and the Wndings are presently being discussed controversially. It has been questioned whether false positive results might have been generated due to sequence homologies or contamination problems for the PCR products and unspeciWc immunohistochemical staining procedures as shown for antigenic sites of host proteins and the chlamydial heat-shock proteins [24][25][26][27][28].…”

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“…This intracellular bacterium has been found at high incidence in the brains of AD patients by PCR and immunohistochemistry [96]. C. pneumoniae has also been found localized in nerve cells in close proximity to neurofibrillary tangles, a characteristic of AD [96,97].…”