Plasma epidermal growth factor levels predict cognitive decline in Parkinson disease.
Plasma epidermal growth factor levels predict cognitive decline in Parkinson disease.
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DOI：
10.1002/ana.22271
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发表时间：
2011-04
影响因子：
11.2
通讯作者：
Trojanowski, John Q.
中科院分区：
文献类型：
--
作者：
Chen-Plotkin, Alice S.;Hu, William T.;Siderowf, Andrew;Weintraub, Daniel;Gross, Rachel Goldmann;Hurtig, Howard I.;Xie, Sharon X.;Arnold, Steven E.;Grossman, Murray;Clark, Christopher M.;Shaw, Leslie M.;McCluskey, Leo;Elman, Lauren;Van Deerlin, Vivianna M.;Lee, Virginia M. -Y.;Soares, Holly;Trojanowski, John Q.
大多数帕金森病 (PD) 患者最终会出现认知障碍 (CI)。然而，认知症状的发作时间和严重程度都无法准确预测。我们寻找基于血浆的 PD 中 CI 生物标志物。招募了 70 名 PD 患者的发现队列。在基线和年度随访时使用 Mattis 痴呆评定量表 2 (DRS) 评估认知状态，并使用基于微珠的免疫测定法测定 102 种蛋白质的基线血浆水平。使用线性回归，我们确定了 PD 中 CI 的生物标志物，即其水平与基线认知表现和/或随访时认知能力下降相关的蛋白质。然后，我们使用不同的技术平台，对 113 名 PD 患者组成的单独队列复制了认知表现与顶级生物标志物水平之间的关联。在发现队列中，十一种蛋白质的血浆水平与基线认知表现相关。最佳候选者是表皮生长因子（EGF，p<0.001）；其他 10 种分析物中的许多与样品中的 EGF 共同变化。低水平的 EGF 不仅与基线时较差的认知测试分数相关，而且还预测对于那些基线认知完好的人，在随访时认知能力下降至痴呆范围 DRS 分数的风险增加八倍。在 113 名 PD 患者的独立复制队列中发现，血浆 EGF 水平与认知能力之间的关系较弱，但仍然显着。我们的数据表明血浆 EGF 可能是 PD 进展至 CI 的生物标志物。
Most people with Parkinson's disease (PD) eventually develop cognitive impairment (CI). However, neither the timing of onset nor the severity of cognitive symptoms can be accurately predicted. We sought plasma-based biomarkers for CI in PD. A discovery cohort of 70 PD patients was recruited. Cognitive status was evaluated with the Mattis Dementia Rating Scale-2 (DRS) at baseline and on annual follow-up visits, and baseline plasma levels of 102 proteins were determined with a bead-based immunoassay. Using linear regression, we identified biomarkers of CI in PD, i.e. proteins whose levels correlated with cognitive performance at baseline and/or cognitive decline at follow-up. We then replicated the association between cognitive performance and levels of the top biomarker, using a different technical platform, with a separate cohort of 113 PD patients. Eleven proteins exhibited plasma levels correlating with baseline cognitive performance in the discovery cohort. The best candidate was epidermal growth factor (EGF, p<0.001); many of the other 10 analytes co-varied with EGF across samples. Low levels of EGF not only correlated with poor cognitive test scores at baseline, but also predicted an eightfold greater risk of cognitive decline to dementia-range DRS scores at follow-up for those with intact baseline cognition. A weaker, but still significant, relationship between plasma EGF levels and cognitive performance was found in an independent replication cohort of 113 PD patients. Our data suggest that plasma EGF may be a biomarker for progression to CI in PD.
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影响因子：
11.2
作者：
Goris, An;Williams-Gray, Caroline H.;Sawcer, Stephen J.
通讯作者：
Sawcer, Stephen J.
影响因子：
11
作者：
HUGHES, AJ;DANIEL, SE;LEES, AJ
通讯作者：
LEES, AJ
DOI：
10.1073/pnas.0700901104
发表时间：
2007-09-04
影响因子：
11.1
作者：
Inoue, Haruhisa;Lin, Ling;Isacson, Ole
通讯作者：
Isacson, Ole
影响因子：
12.7
作者：
Hu WT;Chen-Plotkin A;Arnold SE;Grossman M;Clark CM;Shaw LM;McCluskey L;Elman L;Karlawish J;Hurtig HI;Siderowf A;Lee VM;Soares H;Trojanowski JQ
通讯作者：
Trojanowski JQ
影响因子：
11
作者：
Aarsland, D;Litvan, I;Larsen, JP
通讯作者：
Larsen, JP