Jones T Bucky, Chu Ping, Wilkey Brooke, Lynch Leigha, Jentarra Garilyn
College of Graduate Studies, Midwestern University, Glendale, AZ 85308, USA.
Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308, USA.
Brain Sci. 2024 Jul 3;14(7):677. doi: 10.3390/brainsci14070677.
Alzheimer's disease (AD) is characterized by cognitive decline and neuropathology including amyloid beta (Aβ) plaques and neurofibrillary tangles (tau). Factors initiating or driving these pathologies remain unclear, though microbes have been increasingly implicated. Our data and others' findings indicate that microbes may be common constituents of the brain. It is notable that Aβ and tau have antimicrobial properties, suggesting a response to microbes in the brain. We used 16S rRNA sequencing to compare major bacterial phyla in post-mortem tissues from individuals exhibiting a range of neuropathology and cognitive status in two brain regions variably affected in AD. Our data indicate that strong regional differences exist, driven in part by the varied presence of Proteobacteria and Firmicutes. We confirmed our data using ELISA of bacterial lipopolysaccharide (LPS) and lipoteichoic acid in the same brain tissue. We identified a potential association between the composition of phyla and the presence of neuropathology but not cognitive status. Declining cognition and increasing pathology correlated closely with serum LPS, 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 potentially associated with neurodegenerative pathology.
阿尔茨海默病（AD）的特征是认知能力下降以及神经病理学改变，包括β淀粉样蛋白（Aβ）斑块和神经原纤维缠结（tau）。尽管微生物越来越多地被认为与这些病变有关，但引发或推动这些病变的因素仍不清楚。我们的数据以及其他人的研究结果表明，微生物可能是大脑的常见组成部分。值得注意的是，Aβ和tau具有抗菌特性，这表明大脑对微生物有反应。我们使用16S rRNA测序来比较来自两个在AD中受影响程度不同的脑区、具有一系列神经病理学和认知状态的个体死后组织中的主要细菌门类。我们的数据表明存在强烈的区域差异，部分原因是变形菌门和厚壁菌门的不同存在情况。我们使用酶联免疫吸附测定法（ELISA）检测同一脑组织中的细菌脂多糖（LPS）和脂磷壁酸，从而证实了我们的数据。我们确定了门类组成与神经病理学存在之间的潜在关联，但与认知状态无关。认知能力下降和病变增加与血清LPS密切相关，但与大脑LPS水平无关，尽管大脑LPS与脑淀粉样血管病呈强负相关。总体而言，我们的数据表明脑组织中微生物群体存在区域特异性异质性，这可能与神经退行性病变有关。
