Research press release


Nature Neuroscience

Epigenomic alterations in Alzheimer disease


Philip De Jager、David Bennett、およびJonathan Millたちは、合わせておよそ1200人の個別の患者から得た検死後のAD脳について、ゲノム全体にわたるDNAメチル化の変化をまとめた。それぞれの研究で、メチル化(エピジェネティックな変化のうちDNA発現を示すもの)の程度が健常の対照者に比べて増加または減少している遺伝子領域が11か所および7か所見つかった。これらの遺伝子領域は、アミロイド斑の増大、ADに顕著なタンパク質の形成、臨床で特徴的な神経変性といったAD症状に密接に関連している。そのうち、ANK1、RHBDF2、 RPL13、CDH23の4遺伝子は2つの研究双方に見られ、結果の交差再現となっている。


Specific epigenetic changes - a mechanism by which environmental factors may influence gene expression - in the brain of Alzheimer disease (AD) patients correlate with the pathological symptoms of the disease. These findings, reported in two independent epigenome-wide association papers published online this week in Nature Neuroscience, present new targets for studying the neurobiological basis of AD and developing potential therapies.

Philip De Jager, David Bennett and colleagues, and Jonathan Mill and colleagues profiled DNA methylation changes of postmortem AD brains at a genome-wide scale from a combined total of approximately 1200 distinct patients. The two studies find 11 and 7 gene regions, respectively, that show increased or decreased levels of methylation - a type of epigenetic change indicating DNA expression - when compared healthy controls. These gene regions are significantly associated with AD symptoms such as the proliferation of amyloid plaques, protein formations commonly seen in AD, and clinical features of neurodegeneration. Four of these genes - ANK1, RHBDF2, RPL13 and CDH23 - were found in both studies, thus representing a cross replication of the results.

While the exact cellular functions of these genes are still unclear, these results present new targets to study the neurobiological basis of AD and develop potential therapies. As DNA methylation is a mechanism by which gene expression can be influenced by the environment, these modifications may account for some of the causes of age-related neurodegenerative diseases such as AD, and may also suggest a mechanism by which sporadic forms of the disease can occur.

doi: 10.1038/nn.3782

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