Neuropathological and transcriptomic characteristics of the aged brain
Neuropathological and transcriptomic characteristics of the aged brain
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DOI：
10.7554/elife.31126
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发表时间：
2017-11-09
期刊：
影响因子：
7.7
通讯作者：
Lein, Ed
中科院分区：
文献类型：
--
作者：
Miller, Jeremy A.;Guillozet-Bongaarts, Angela;Lein, Ed
随着越来越多的人寿命延长，与年龄相关的神经退行性疾病日益成为一个重要的社会健康问题。针对阿尔茨海默病（AD）中β淀粉样蛋白等特定病理的治疗尚未导致有效的治疗，而且越来越多的证据表明，随着年龄的增长，传统病理与认知能力之间存在脱节，这表明个体对病理的适应能力存在差异。在这里，我们对107名老年供体（中位数= 90）的海马和两个区域皮质进行了全面的神经病理学、分子和转录组学表征，这些供体来自成人思维变化（ACT）研究，作为免费资源（http://aging,brain-map,org/）。我们确认了阿尔茨海默病病理与痴呆之间的既定关联，尽管可能与年龄相关的变异性增加，并确定了与病理性tau和炎症标志物相关的共表达基因组。最后，我们证明了痴呆症和RNA质量之间的关系，并发现了共同的基因特征，强调了在研究痴呆症时适当控制RNA质量的重要性。
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.