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阿尔茨海默病和帕金森病相关脑区的高分辨率16S rRNA基因二代测序研究

High resolution 16S rRNA gene Next Generation Sequencing study of brain areas associated with Alzheimer's and Parkinson's disease.

作者信息

Emery David C, Davies Maria, Cerajewska Tanya L, Taylor Jelena, Hazell Mae, Paterson Alex, Allen-Birt Shelley J, West Nicola X

机构信息

Bristol Dental School, Bristol, United Kingdom.

Translational Health Sciences, Learning and Research, Bristol Medical School, Southmead Hospital, Bristol, United Kingdom.

出版信息

Front Aging Neurosci. 2022 Dec 9;14:1026260. doi: 10.3389/fnagi.2022.1026260. eCollection 2022.

Abstract

INTRODUCTION

Alzheimer's (AD) and Parkinson's disease (PD) are neurodegenerative conditions characterized by incremental deposition of β-amyloid (Aβ) and α-synuclein in AD and PD brain, respectively, in relatively conserved patterns. Both are associated with neuroinflammation, with a proposed microbial component for disease initiation and/or progression. Notably, Aβ and α-synuclein have been shown to possess antimicrobial properties. There is evidence for bacterial presence within the brain, including the oral pathobiont , with cognitive impairment and brain pathology being linked to periodontal (gum) disease and gut dysbiosis.

METHODS

Here, we use high resolution 16S rRNA PCR-based Next Generation Sequencing (16SNGS) to characterize bacterial composition in brain areas associated with the early, intermediate and late-stage of the diseases.

RESULTS AND DISCUSSION

This study reveals the widespread presence of bacteria in areas of the brain associated with AD and PD pathology, with distinctly different bacterial profiles in blood and brain. Brain area profiles were overall somewhat similar, predominantly oral, with some bacteria subgingival and oronasal in origin, and relatively comparable profiles in AD and PD brain. However, brain areas associated with early disease development, such as the locus coeruleus, were substantially different in bacterial DNA content compared to areas affected later in disease etiology.

摘要

引言

阿尔茨海默病(AD)和帕金森病(PD)是神经退行性疾病,其特征分别是在AD和PD大脑中β-淀粉样蛋白(Aβ)和α-突触核蛋白以相对保守的模式逐渐沉积。两者都与神经炎症有关,有一种假说认为微生物成分在疾病的起始和/或进展中起作用。值得注意的是,Aβ和α-突触核蛋白已被证明具有抗菌特性。有证据表明大脑中存在细菌,包括口腔致病共生菌,认知障碍和脑病理学与牙周(牙龈)疾病和肠道菌群失调有关。

方法

在此,我们使用基于高分辨率16S rRNA PCR的下一代测序(16SNGS)来表征与疾病早期、中期和晚期相关的脑区中的细菌组成。

结果与讨论

本研究揭示了与AD和PD病理学相关的脑区中广泛存在细菌,血液和大脑中的细菌谱明显不同。脑区谱总体上有些相似,主要来自口腔,一些细菌起源于龈下和口鼻部位,AD和PD大脑中的谱相对可比。然而,与疾病早期发展相关的脑区,如蓝斑,与疾病病因后期受影响的区域相比,细菌DNA含量有很大差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8f0/9780557/12b151e21ca1/fnagi-14-1026260-g001.jpg

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