Miklossy Judith, Khalili Kamel, Gern Lise, Ericson Rebecca L, Darekar Pushpa, Bolle Lorie, Hurlimann Jean, Paster Bruce J
University Institute of Pathology, Division of Neuropathology, University Medical School (CHUV), 1011, Lausanne, Switzerland.
J Alzheimers Dis. 2004 Dec;6(6):639-49; discussion 673-81. doi: 10.3233/jad-2004-6608.
The cause, or causes, of the vast majority of Alzheimer's disease cases are unknown. A number of contributing factors have been postulated, including infection. It has long been known that the spirochete Treponema pallidum, which is the infective agent for syphilis, can in its late stages cause dementia, chronic inflammation, cortical atrophy and amyloid deposition. Spirochetes of unidentified types and strains have previously been observed in the blood, CSF and brain of 14 AD patients tested and absent in 13 controls. In three of these AD cases spirochetes were grown in a medium selective for Borrelia burgdorferi. In the present study, the phylogenetic analysis of these spirochetes was made. Positive identification of the agent as Borrelia burgdorferi sensu stricto was based on genetic and molecular analyses. Borrelia antigens and genes were co-localized with beta-amyloid deposits in these AD cases. The data indicate that Borrelia burgdorferi may persist in the brain and be associated with amyloid plaques in AD. They suggest that these spirochetes, perhaps in an analogous fashion to Treponema pallidum, may contribute to dementia, cortical atrophy and amyloid deposition. Further in vitro and in vivo studies may bring more insight into the potential role of spirochetes in AD.
绝大多数阿尔茨海默病病例的病因尚不清楚。人们已经提出了一些促成因素,包括感染。长期以来,人们都知道梅毒的病原体苍白密螺旋体在晚期可导致痴呆、慢性炎症、皮质萎缩和淀粉样蛋白沉积。在对14例接受检测的阿尔茨海默病患者的血液、脑脊液和大脑中,此前观察到了未明确类型和菌株的螺旋体,而在13名对照者中未观察到。在其中3例阿尔茨海默病病例中,螺旋体在一种对伯氏疏螺旋体有选择性的培养基中生长。在本研究中,对这些螺旋体进行了系统发育分析。基于基因和分子分析,将病原体明确鉴定为狭义的伯氏疏螺旋体。在这些阿尔茨海默病病例中,伯氏疏螺旋体抗原和基因与β淀粉样蛋白沉积物共定位。数据表明,伯氏疏螺旋体可能在大脑中持续存在,并与阿尔茨海默病中的淀粉样斑块相关。这些数据提示,这些螺旋体可能以类似于苍白密螺旋体的方式,导致痴呆、皮质萎缩和淀粉样蛋白沉积。进一步的体外和体内研究可能会更深入地了解螺旋体在阿尔茨海默病中的潜在作用。