Department of Biology and Environmental Sciences, University of New Haven, West Haven, CT, USA.
Molecular Interrogation Research Laboratory, Naples, FL, USA.
J Alzheimers Dis. 2022;85(2):889-903. doi: 10.3233/JAD-215398.
Infections by bacterial or viral agents have been hypothesized to influence the etiology of neurodegenerative diseases.
This study examined the potential presence of Borrelia burgdorferi spirochete, the causative agent of Lyme disease, in brain autopsy tissue of patients diagnosed with either Alzheimer's (AD) or Parkinson's diseases.
Brain tissue sections from patients with age-matched controls were evaluated for antigen and DNA presence of B. burgdorferi using various methods. Positive Borrelia structures were evaluated for co-localization with biofilm and AD markers such as amyloid and phospho-tau (p-Tau) using immunohistochemical methods.
The results showed the presence of B. burgdorferi antigen and DNA in patients with AD pathology and among those, one of them was previously diagnosed with Lyme disease. Interestingly, a significant number of Borrelia-positive aggregates with a known biofilm marker, alginate, were found along with the spirochetal structures. Our immunohistochemical data also showed that Borrelia-positive aggregates co-localized with amyloid and phospho-tau markers. To further prove the potential relationship of B. burgdorferi and amyloids, we infected two mammalian cell lines with B. burgdorferi which resulted in a significant increase in the expression of amyloid-β and p-Tau proteins in both cells lines post-infection.
These results indicate that B. burgdorferi can be found in AD brain tissues, not just in spirochete but a known antibiotics resistant biofilm form, and its co-localized amyloid markers. In summary, this study provides evidence for a likely association between B. burgdorferi infections and biofilm formation, AD pathology, and chronic neurodegenerative diseases.
细菌或病毒感染被认为会影响神经退行性疾病的病因。
本研究检测了伯氏疏螺旋体(莱姆病的病原体)在诊断为阿尔茨海默病(AD)或帕金森病的患者脑尸检组织中的潜在存在。
使用各种方法评估年龄匹配的对照患者的脑组织切片中伯氏疏螺旋体的抗原和 DNA 存在情况。使用免疫组织化学方法评估阳性博氏疏螺旋体结构与生物膜和 AD 标志物(如淀粉样蛋白和磷酸化 tau(p-Tau))的共定位。
结果显示,AD 病理患者和其中一位曾被诊断患有莱姆病的患者存在伯氏疏螺旋体抗原和 DNA。有趣的是,在螺旋体结构旁边发现了大量带有已知生物膜标志物藻酸盐的伯氏疏螺旋体阳性聚集物。我们的免疫组织化学数据还表明,伯氏疏螺旋体阳性聚集物与淀粉样蛋白和磷酸化 tau 标志物共定位。为了进一步证明伯氏疏螺旋体和淀粉样蛋白之间的潜在关系,我们用伯氏疏螺旋体感染了两种哺乳动物细胞系,感染后两种细胞系中淀粉样蛋白-β和 p-Tau 蛋白的表达显著增加。
这些结果表明,伯氏疏螺旋体可以在 AD 脑组织中找到,不仅是在螺旋体中,而且是在已知的抗生素耐药生物膜形式中,以及其共定位的淀粉样蛋白标志物。总之,这项研究为伯氏疏螺旋体感染与生物膜形成、AD 病理学和慢性神经退行性疾病之间可能存在关联提供了证据。