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老年人大脑的神经病理学和转录组学特征。

Neuropathological and transcriptomic characteristics of the aged brain.

机构信息

Allen Institute for Brain Science, Seattle, United States.

Department of Medicine, University of Washington, Seattle, United States.

出版信息

Elife. 2017 Nov 9;6:e31126. doi: 10.7554/eLife.31126.

DOI:10.7554/eLife.31126
PMID:29120328
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5679757/
Abstract

As more people live longer, age-related neurodegenerative diseases are an increasingly important societal health issue. Treatments targeting specific pathologies such as amyloid beta in Alzheimer's disease (AD) have not led to effective treatments, and there is increasing evidence of a disconnect between traditional pathology and cognitive abilities with advancing age, indicative of individual variation in resilience to pathology. Here, we generated a comprehensive neuropathological, molecular, and transcriptomic characterization of hippocampus and two regions cortex in 107 aged donors (median = 90) from the Adult Changes in Thought (ACT) study as a freely-available resource (http://aging.brain-map.org/). We confirm established associations between AD pathology and dementia, albeit with increased, presumably aging-related variability, and identify sets of co-expressed genes correlated with pathological tau and inflammation markers. Finally, we demonstrate a relationship between dementia and RNA quality, and find common gene signatures, highlighting the importance of properly controlling for RNA quality when studying dementia.

摘要

随着越来越多的人长寿，与年龄相关的神经退行性疾病是一个日益重要的社会健康问题。针对特定病理学的治疗方法，如阿尔茨海默病（AD）中的淀粉样蛋白β，并没有导致有效的治疗方法，而且越来越多的证据表明，传统病理学与年龄增长时的认知能力之间存在脱节，这表明个体对病理学的适应能力存在差异。在这里，我们对 107 名年龄在（中位数=90）的成年人变化思维（ACT）研究中的海马体和两个皮质区域进行了全面的神经病理学、分子和转录组学特征分析，作为一个免费资源（http://aging.brain-map.org/）。我们证实了 AD 病理学与痴呆之间的关联，尽管存在增加的、可能与衰老相关的变异性，并且确定了与病理性 tau 和炎症标志物相关的共同表达基因集。最后，我们证明了痴呆与 RNA 质量之间的关系，并发现了常见的基因特征，这突出了在研究痴呆症时正确控制 RNA 质量的重要性。

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