Identification and localization of Chlamydia pneumoniae in the Alzheimer's brain
Identification and localization of Chlamydia pneumoniae in the Alzheimer's brain
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DOI：
10.1007/s004300050071
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发表时间：
1998-06-01
影响因子：
5.4
通讯作者：
Hudson, AP
中科院分区：
文献类型：
--
作者：
Balin, BJ;Gerard, HC;Hudson, AP
我们评估了迟发性阿尔茨海默病(AD)患者和非迟发性阿尔茨海默病(AD)患者的死后脑样本中是否存在细胞内肺炎衣原体，因为一些间接证据似乎表明，感染这种微生物可能与疾病有关。从这些样本中提取的核酸通过聚合酶链式反应(PCR)对细菌的DNA序列进行筛选，这样的分析表明，在19例AD患者中，具有典型AD相关神经病理的脑区有17例细菌呈阳性。对18/19名对照组患者相同脑区的相似分析均为PCR阴性。对阿尔茨海默病脑区组织的电子和免疫电子显微镜研究发现，衣原体基本小体和网状小体，但非阿尔茨海默病大脑的类似检查结果为阴性。对一部分受感染的AD脑组织进行的肺炎链球菌培养研究呈强阳性，而对非AD脑组织进行的相同分析为阴性。使用AD大脑感染区域的RNA进行的逆转录(RT)-PCR分析证实，在这些样本中存在两个重要的肺炎衣原体基因的转录本，但在对照组中没有。对阿尔茨海默病患者的大脑进行免疫组织化学检查，发现肺炎衣原体存在于周细胞、小胶质细胞和星形胶质细胞内，而不是对照组。进一步的免疫标记研究证实了细菌主要存在于AD脑中的神经病理区域，因此，肺炎衣原体在AD脑中的神经病理区域中存在、存活并转录活跃，这可能表明该微生物的感染是迟发性AD的一个危险因素。
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.