Metabolome in progression to Alzheimer's disease.
Metabolome in progression to Alzheimer's disease.
复制标题
DOI：
10.1038/tp.2011.55
复制
发表时间：
2011-12-13
影响因子：
6.8
通讯作者：
Soininen H
中科院分区：
文献类型：
--
作者：
Orešič M;Hyötyläinen T;Herukka SK;Sysi-Aho M;Mattila I;Seppänan-Laakso T;Julkunen V;Gopalacharyulu PV;Hallikainen M;Koikkalainen J;Kivipelto M;Helisalmi S;Lötjönen J;Soininen H
轻度认知功能障碍（MCI）被认为是正常衰老和阿尔茨海默病（AD）之间的过渡阶段。MCI赋予发展AD的风险增加，尽管状态是异质的，具有几种可能的结果，包括甚至恢复到正常认知。我们试图在一项前瞻性研究中确定与AD进展和诊断相关的血清代谢组学特征。在基线评估时，入组研究的受试者被分为三个诊断组：健康对照组（n=46）、MCI组（n=143）和AD组（n=47）。在MCI受试者中，52例在随访中进展为AD。应用综合代谢组学方法分析基线血清样本，并将基线和随访时的代谢产物谱与诊断相关联。在基线时，AD患者的特征是醚磷脂、磷脂酰胆碱、鞘磷脂和甾醇减少。鉴定了包含三种代谢物的分子特征，其预测了随访中进展为AD。预测模型的主要贡献者是2，4-二羟基丁酸，其在AD进展者中上调（P=0.0048），表明缺氧可能参与早期AD发病机制。代谢组学数据的通路分析支持了这一点，该分析确定了后来进展为AD的患者中戊糖磷酸通路的上调。总之，我们的研究结果主要涉及缺氧，氧化应激，以及膜脂质重塑进展到AD。建立预测性生物标志物（如我们的）的致病相关性不仅可以促进早期诊断，还可以帮助确定新的治疗途径。
Mild cognitive impairment (MCI) is considered as a transition phase between normal aging and Alzheimer's disease (AD). MCI confers an increased risk of developing AD, although the state is heterogeneous with several possible outcomes, including even improvement back to normal cognition. We sought to determine the serum metabolomic profiles associated with progression to and diagnosis of AD in a prospective study. At the baseline assessment, the subjects enrolled in the study were classified into three diagnostic groups: healthy controls (n=46), MCI (n=143) and AD (n=47). Among the MCI subjects, 52 progressed to AD in the follow-up. Comprehensive metabolomics approach was applied to analyze baseline serum samples and to associate the metabolite profiles with the diagnosis at baseline and in the follow-up. At baseline, AD patients were characterized by diminished ether phospholipids, phosphatidylcholines, sphingomyelins and sterols. A molecular signature comprising three metabolites was identified, which was predictive of progression to AD in the follow-up. The major contributor to the predictive model was 2,4-dihydroxybutanoic acid, which was upregulated in AD progressors (P=0.0048), indicating potential involvement of hypoxia in the early AD pathogenesis. This was supported by the pathway analysis of metabolomics data, which identified upregulation of pentose phosphate pathway in patients who later progressed to AD. Together, our findings primarily implicate hypoxia, oxidative stress, as well as membrane lipid remodeling in progression to AD. Establishment of pathogenic relevance of predictive biomarkers such as ours may not only facilitate early diagnosis, but may also help identify new therapeutic avenues.
登录
查看更多内容
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
7.4
作者：
Castillo, Sandra;Mattila, Ismo;Hyotylainen, Tuulia
通讯作者：
Hyotylainen, Tuulia
影响因子：
4.2
作者：
He, Xingxuan;Huang, Yu;Schuchman, Edward H.
通讯作者：
Schuchman, Edward H.
影响因子：
3.5
作者：
Hänninen, T;Hallikainen, M;Soininen, H
通讯作者：
Soininen, H
影响因子：
4.7
作者：
HAKIM, AM;MOSS, G;GOLLOMP, SM
通讯作者：
GOLLOMP, SM