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一种新型的基于血浆的阿尔茨海默病生物标志物。

A Novel Plasma Based Biomarker of Alzheimer's Disease.

作者信息

Bradley-Whitman Melissa A, Abner Erin, Lynn Bert C, Lovell Mark A

机构信息

Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA.

Department of Epidemiology, University of Kentucky, Lexington, KY, USA.

出版信息

J Alzheimers Dis. 2015;47(3):761-71. doi: 10.3233/JAD-150183.

Abstract

Specific biomarkers in a readily accessible biological fluid, such as blood, could aid in the identification, characterization, validation, and routine monitoring of Alzheimer's disease (AD) progression. In the current study, levels of the previously described novel cerebrospinal fluid aberrant protein complex composed of prostaglandin-D-synthase (PDS) and transthyretin (TTR) were quantified in plasma by a custom two-probe sandwich ELISA and compared to amyloid-β (Aβ)(1-42) as a standard plasma biomarker of AD. Plasma was analyzed from 140 probable AD subjects, 135 subjects with mild cognitive impairment (MCI), 74 normal control subjects (NC) prior to MCI transition, 23 diseased control (DC) subjects with either frontotemporal dementia or dementia with Lewy bodies, and 182 normal control (NC) subjects who did not progress to MCI or dementia. Levels of Aβ(1-42) were significantly elevated in NC subjects prior to MCI conversion but significantly reduced in probable AD subjects compared to NC subjects. Similarly, levels of the PDS-TTR complex were significantly reduced in both MCI and probable AD subjects compared to NC subjects. Furthermore, levels of Aβ(1-42) and the PDS-TTR complex were not significantly different in DC subjects compared to NC subjects. MMSE scores were weakly but significantly correlated with plasma levels of the PDS-TTR complex and Aβ(1-42). Trail B scores were weakly but significantly correlated with plasma levels of Aβ(1-42). Comparison of receiver operating curves shows the PDS-TTR complex is comparable to Aβ(1-42) in both MCI and probable AD subjects.

摘要

血液等易于获取的生物流体中的特定生物标志物,有助于阿尔茨海默病(AD)进展的识别、特征描述、验证及常规监测。在本研究中,通过定制的双探针夹心酶联免疫吸附测定法(ELISA)对血浆中由前列腺素-D-合酶(PDS)和转甲状腺素蛋白(TTR)组成的先前描述的新型脑脊液异常蛋白复合物水平进行定量,并与作为AD标准血浆生物标志物的淀粉样β蛋白(Aβ)(1-42)进行比较。分析了140例可能患有AD的受试者、135例轻度认知障碍(MCI)受试者、74例在转变为MCI之前的正常对照受试者(NC)、23例患有额颞叶痴呆或路易体痴呆的疾病对照(DC)受试者以及182例未进展为MCI或痴呆的正常对照(NC)受试者的血浆。与NC受试者相比,Aβ(1-42)水平在MCI转化前的NC受试者中显著升高,但在可能患有AD的受试者中显著降低。同样,与NC受试者相比,MCI和可能患有AD的受试者中PDS-TTR复合物水平均显著降低。此外,与NC受试者相比,DC受试者中Aβ(1-42)和PDS-TTR复合物水平无显著差异。简易精神状态检查表(MMSE)评分与PDS-TTR复合物和Aβ(1-42)的血浆水平呈弱但显著的相关性。B部分连线测验(Trail B)评分与Aβ(1-42)的血浆水平呈弱但显著的相关性。受试者工作特征曲线的比较表明,在MCI和可能患有AD的受试者中,PDS-TTR复合物与Aβ(1-42)相当。

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