Age-Correlated Gene Expression in Normal and Neurodegenerative Human Brain Tissues
Age-Correlated Gene Expression in Normal and Neurodegenerative Human Brain Tissues
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DOI：
10.1371/journal.pone.0013098
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发表时间：
2010-09-29
期刊：
影响因子：
3.7
通讯作者：
Wang, Li-San
中科院分区：
文献类型：
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作者：
Cao, Kajia;Chen-Plotkin, Alice S.;Wang, Li-San
工作背景：人类大脑衰老受到特别关注，部分原因是老年人患阿尔茨海默病等神经退行性疾病的风险增加。最近的技术进步使我们能够调查是否类似的机制的基础老化和神经退行性变，通过量化的相似性和差异，在其全基因组的基因表达profiles.Principal Findings：我们已经开发了一种计算方法，用于评估一个人的“生理大脑年龄”通过比较全球mRNA表达数据集在一系列正常的人脑样本。将这种方法应用于两种疾病-阿尔茨海默病的选定区域的大脑样本（AD，上级额回），额颞叶变性（FTLD，在额叶皮质的喙侧方面，类似于BA 10）-显示虽然对照组在生理年龄和实足年龄之间没有表现出显著差异，但FTLD和AD表现出过早老化的表达谱。这项研究建立了一个定量量表来测量神经退行性疾病队列中的过早衰老，并确定了衰老和某些形式的神经退行性疾病共同的特定生理机制。此外，与AD和FTLD相关的加速表达谱表明了发展这些疾病风险的一些共同机制。
Background: Human brain aging has received special attention in part because of the elevated risks of neurodegenerative disorders such as Alzheimer's disease in seniors. Recent technological advances enable us to investigate whether similar mechanisms underlie aging and neurodegeneration, by quantifying the similarities and differences in their genome-wide gene expression profiles.Principal Findings: We have developed a computational method for assessing an individual's "physiological brain age'' by comparing global mRNA expression datasets across a range of normal human brain samples. Application of this method to brains samples from select regions in two diseases - Alzheimer's disease (AD, superior frontal gyrus), frontotemporal lobar degeneration (FTLD, in rostral aspect of frontal cortex, similar to BA10) - showed that while control cohorts exhibited no significant difference between physiological and chronological ages, FTLD and AD exhibited prematurely aged expression profiles.Conclusions: This study establishes a quantitative scale for measuring premature aging in neurodegenerative disease cohorts, and it identifies specific physiological mechanisms common to aging and some forms of neurodegeneration. In addition, accelerated expression profiles associated with AD and FTLD suggest some common mechanisms underlying the risk of developing these diseases.