Regional differences in microbial infiltration of brain tissue from Alzheimer’s disease patients and control individuals

R-code and raw data for the associated study. Abstract below:Alzheimer’s disease (AD) is characterized by dementia and neuropathology including amyloid beta (Ab) plaques and neurofibrillary tangles. It is not understood what initiates or drives these pathologies however, recently, microbes have been increasingly implicated. Microbes may be a regular constituent of the brain and Ab and tau have been shown to have antimicrobial properties. We used 16S rRNA sequencing to compare major bacterial phyla in post-mortem tissues of individuals exhibiting a range of neuropathology and cognitive status in two brain regions variably affected in AD. We confirmed our data using ELISA of bacterial lipopolysaccharide (LPS) and lipoteichoic acid in the same brain tissue and compared it to serum LPS from those individuals. We found significant differences in bacterial taxa present in different brain regions that were associated more with pathology than with cognitive status. Specifically, individuals with higher levels of pathology showed a loss of diversity compared to individuals who did not have pathology. Declining cognition and increasing pathology correlated closely with serum, but not brain levels of LPS, although brain LPS showed a strong negative correlation with cerebral amyloid angiopathy. Collectively, our data suggest a region-specific heterogeneity of microbial populations in brain tissue that may be associated with pathology.

本关联研究的R代码与原始数据。摘要如下：阿尔茨海默病（Alzheimer’s Disease, AD）以痴呆症及神经病理特征为主要表现，包括β淀粉样蛋白（Amyloid Beta, Aβ）斑块与神经原纤维缠结。目前尚不明确此类病理改变的起始与驱动因素，但近年来微生物愈发被认为与该病存在关联。微生物或可成为大脑的正常组成成分，且β淀粉样蛋白与tau蛋白（Tau Protein）已被证实具有抗菌特性。本研究采用16S核糖体RNA（16S rRNA）测序技术，对比了阿尔茨海默病不同受累程度的两个脑区中，具有不同神经病理程度与认知状态的个体的死后脑组织内主要细菌门类的差异。我们通过对同一脑组织样本中的细菌脂多糖（Lipopolysaccharide, LPS）与脂磷壁酸（Lipoteichoic Acid, LTA）进行酶联免疫吸附试验（Enzyme-Linked Immunosorbent Assay, ELISA）验证了测序数据，并将该检测结果与受试者的血清LPS水平进行了对比分析。研究发现，不同脑区的细菌分类群存在显著差异，且此类差异与神经病理程度的相关性高于与认知状态的相关性。具体而言，神经病理程度较高的个体，其脑组织内细菌多样性较无病理改变的个体出现了下降。认知功能衰退与病理程度加重仅与血清LPS水平密切相关，与脑组织LPS水平无明显关联；尽管脑组织LPS水平与脑淀粉样血管病（Cerebral Amyloid Angiopathy, CAA）呈显著负相关。综合来看，本研究数据表明脑组织内微生物群存在脑区特异性异质性，且该异质性或与神经病理改变相关。