An inflammatory and trophic disconnect biomarker profile revealed in Down syndrome plasma: Relation to cognitive decline and longitudinal evaluation
An inflammatory and trophic disconnect biomarker profile revealed in Down syndrome plasma: Relation to cognitive decline and longitudinal evaluation
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DOI：
10.1016/j.jalz.2016.05.001
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发表时间：
2016-11-01
影响因子：
14
通讯作者：
Cuello, A. Claudio
中科院分区：
文献类型：
--
作者：
Iulita, M. Florencia;Ower, Alison;Cuello, A. Claudio
简介：鉴于阿尔茨海默氏病的病理发展沉默了几十年的唐氏综合征（DS），痴呆的预后生物标志物是一个主要的need.Methods：我们调查了A β，神经生长因子原，tPA，神经丝氨酸蛋白酶，金属蛋白酶和炎症分子在31个人与DS（有和无痴呆）和31名健康对照的血浆水平。我们研究了生物标志物和认知能力下降之间的关联。结果：与对照组相比，DS血浆中的A β 40和A β 42升高，即使在没有痴呆的DS个体中也是如此。血浆A β与2年内认知能力下降率相关。即使在AD-无症状阶段，DS血浆中ProNGF、MMP-1、MMP-3、MMP-9活性、TNF-α、IL-6和IL-10也较高。血浆A β 42水平下降和proNGF水平升高与认知能力下降相关。A β和炎症分子的联合措施是一个强有力的预测前瞻性认知deficitation.Conclusions：我们的研究结果支持相结合的血浆和认知评估的DS个人痴呆症的风险识别。(C)2016年阿尔茨海默氏症协会。爱思唯尔公司出版All rights reserved.
Introduction: Given that Alzheimer's pathology develops silently over decades in Down syndrome (DS), prognostic biomarkers of dementia are a major need.Methods: We investigated the plasma levels of A beta, proNGF, tPA, neuroserpin, metallo-proteases and inflammatory molecules in 31 individuals with DS (with and without dementia) and in 31 healthy controls. We examined associations between biomarkers and cognitive decline.Results: A beta 40 and A beta 42 were elevated in DS plasma compared to controls, even in DS individuals without dementia. Plasma A beta correlated with the rate of cognitive decline across 2 years. ProNGF, MMP-1, MMP-3, MMP-9 activity, TNF-alpha, IL-6, and IL-10 were higher in DS plasma, even at AD-asymptomatic stages. Declining plasma A beta 42 and increasing proNGF levels correlated with cognitive decline. A combined measure of A beta and inflammatory molecules was a strong predictor of prospective cognitive deterioration.Conclusions: Our findings support the combination of plasma and cognitive assessments for the identification of DS individuals at risk of dementia. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.