Department of Molecular Neuroscience, Institute of Neurology, University College London, London, United Kingdom.
Basic Medical Science Department, Kulliyyah of Medicine, International Islamic University Malaysia, Kuantan, Pahang, Malaysia.
PLoS One. 2023 Feb 24;18(2):e0277630. doi: 10.1371/journal.pone.0277630. eCollection 2023.
Alzheimer's disease is the most common neurological disease worldwide. Unfortunately, there are currently no effective treatment methods nor early detection methods. Furthermore, the disease underlying molecular mechanisms are poorly understood. Global bulk gene expression profiling suggested that the disease is governed by diverse transcriptional regulatory networks. Thus, to identify distinct transcriptional networks impacted into distinct neuronal populations in Alzheimer, we surveyed gene expression differences in over 25,000 single-nuclei collected from the brains of two Alzheimer's in disease patients in Braak stage I and II and age- and gender-matched controls hippocampal brain samples. APOE status was not measured for this study samples (as well as CERAD and THAL scores). Our bioinformatic analysis identified discrete glial, immune, neuronal and vascular cell populations spanning Alzheimer's disease and controls. Astrocytes and microglia displayed the greatest transcriptomic impacts, with the induction of both shared and distinct gene programs.
阿尔茨海默病是全球最常见的神经退行性疾病。不幸的是，目前尚无有效的治疗方法和早期检测方法。此外，疾病的潜在分子机制也知之甚少。全基因组表达谱分析表明，该疾病受多种转录调控网络的控制。因此，为了确定不同的转录网络影响阿尔茨海默病不同的神经元群体，我们调查了来自两名阿尔茨海默病患者（Braak 分期 I 和 II）和年龄及性别匹配的对照海马脑样本的超过 25000 个单个核的基因表达差异。本研究样本未测量 APOE 状态（以及 CERAD 和 THAL 评分）。我们的生物信息学分析确定了跨越阿尔茨海默病和对照组的离散的神经胶质、免疫、神经元和血管细胞群体。星形胶质细胞和小胶质细胞显示出最大的转录组影响，诱导了共同和独特的基因程序。
