Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria.
Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria.
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DOI：
10.1186/1742-2094-8-90
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发表时间：
2011-08-04
影响因子：
9.3
通讯作者：
Miklossy J
中科院分区：
文献类型：
--
作者：
Miklossy J
已证实慢性螺旋体感染可导致慢性进行性痴呆、脑萎缩和晚期神经梅毒的淀粉样蛋白沉积。近年来研究表明，多种螺旋体与梅毒螺旋体相似，可引起痴呆，并可能参与阿尔茨海默病（AD）的发病机制。在这里，我们回顾了文献中关于AD中螺旋体检测的所有数据，并严格分析了螺旋体与AD之间的关联和因果关系，并遵循Koch和Hill的既定标准。结果显示螺旋体与AD之间存在统计学显著相关性（P = 1.5 × 10-17，OR = 20，95%CI = 8-60，N = 247）。当使用中性技术识别所有类型的螺旋体时，或者分析高度流行的牙周病原体密螺旋体时，在超过90%的AD病例中观察到大脑中的螺旋体。在分析的AD病例中，25.3%的患者大脑中检测到伯氏疏螺旋体，与对照组相比，AD患者的发病率高出13倍。牙周病病原体密螺旋体（T. pectinovorum、裂腹叶蜂T. amylovorum、食淀粉T. lecithinolyticum、T. maltophilum、嗜麦芽窄食单胞菌T. medium，T. socranskii）和伯氏疏螺旋体。重要的是，在AD中发生与几种螺旋体的共感染。AD的病理学和生物学特征通过将哺乳动物细胞暴露于螺旋体而在体外再现。根据Koch和Hill的假设，对回顾性数据的分析表明神经螺旋体病和AD之间可能存在因果关系。持续的炎症和淀粉样蛋白沉积发起和持续的慢性螺旋体感染形式与各种假说一起提出了在AD的发病机制中发挥作用的综合实体。正如希尔所建议的，一旦因果关系的可能性确定，就需要立即采取行动。应支持和重视这一领域的AD研究。螺旋体感染发生在痴呆症表现之前的几年或几十年。由于有足够的抗生素和抗炎疗法，如梅毒，人们可能会预防和根除痴呆症。
It is established that chronic spirochetal infection can cause slowly progressive dementia, brain atrophy and amyloid deposition in late neurosyphilis. Recently it has been suggested that various types of spirochetes, in an analogous way to Treponema pallidum, could cause dementia and may be involved in the pathogenesis of Alzheimer's disease (AD). Here, we review all data available in the literature on the detection of spirochetes in AD and critically analyze the association and causal relationship between spirochetes and AD following established criteria of Koch and Hill. The results show a statistically significant association between spirochetes and AD (P = 1.5 × 10-17, OR = 20, 95% CI = 8-60, N = 247). When neutral techniques recognizing all types of spirochetes were used, or the highly prevalent periodontal pathogen Treponemas were analyzed, spirochetes were observed in the brain in more than 90% of AD cases. Borrelia burgdorferi was detected in the brain in 25.3% of AD cases analyzed and was 13 times more frequent in AD compared to controls. Periodontal pathogen Treponemas (T. pectinovorum, T. amylovorum, T. lecithinolyticum, T. maltophilum, T. medium, T. socranskii) and Borrelia burgdorferi were detected using species specific PCR and antibodies. Importantly, co-infection with several spirochetes occurs in AD. The pathological and biological hallmarks of AD were reproduced in vitro by exposure of mammalian cells to spirochetes. The analysis of reviewed data following Koch's and Hill's postulates shows a probable causal relationship between neurospirochetosis and AD. Persisting inflammation and amyloid deposition initiated and sustained by chronic spirochetal infection form together with the various hypotheses suggested to play a role in the pathogenesis of AD a comprehensive entity. As suggested by Hill, once the probability of a causal relationship is established prompt action is needed. Support and attention should be given to this field of AD research. Spirochetal infection occurs years or decades before the manifestation of dementia. As adequate antibiotic and anti-inflammatory therapies are available, as in syphilis, one might prevent and eradicate dementia.
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影响因子：
3.4
作者：
Barcena-Uribarri, Ivan;Thein, Marcus;Benz, Roland
通讯作者：
Benz, Roland
影响因子：
2.5
作者：
ALLEN, JS;MURPHY, GM;TINKLENBERG, JR
通讯作者：
TINKLENBERG, JR
影响因子：
5.4
作者：
Balin, BJ;Gerard, HC;Hudson, AP
通讯作者：
Hudson, AP
DOI：
10.1111/j.1749-6632.1993.tb23057.x
发表时间：
1993-01-01
期刊：
ALZHEIMERS DISEASE: AMYLOID PRECUSOR PROTEINS, SIGNAL TRANSDUCTION, AND NEURONAL TRANSPLANTATION
影响因子：
--
作者：
BAKER, HF;RIDLEY, RM;BRUTON, CJ
通讯作者：
BRUTON, CJ
影响因子：
4.4
作者：
Bulut, Y;Faure, E;Arditi, M
通讯作者：
Arditi, M