Processing of the Platelet Amyloid Precursor Protein in the Mild Cognitive Impairment (MCI)
Processing of the Platelet Amyloid Precursor Protein in the Mild Cognitive Impairment (MCI)
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DOI：
10.1007/s11064-013-1039-7
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发表时间：
2013-07-01
影响因子：
4.4
通讯作者：
Maria Villar, Angel
中科院分区：
文献类型：
--
作者：
Bermejo-Bescos, Paloma;Martin-Aragon, Sagrario;Maria Villar, Angel
有研究表明，轻度认知障碍(MCI)患者的病情恶化速度快于健康的老年人口，并增加了患痴呆症的风险。某些血液分子生物标志物已被确定为阿尔茨海默病(AD)的预后标志物。本研究旨在评估MCI和AD患者的血小板淀粉样前体蛋白(APP)代谢状态，并确定任何变异在多大程度上可以预测MCI患者预测AD的价值。用免疫印迹法检测34例MCI患者和45例AD患者与28例健康老年人血小板中APP、β-APP裂解酶1(BACE1)、早老素1(PS1)、去整合素和金属蛋白酶-10(ADAM-10)的蛋白水平，并用特定的荧光底物检测BACE1和γ-分泌酶的活性。在健康老年人和MCI患者中，BACE1和PS1水平也发现了类似的模式。与健康老年人相比，MCI和AD患者APP水平降低。与年龄匹配的对照组相比，MCI和AD患者的ADAM-10水平均升高。MCI组ADAM-10/BACE1比值高于AD组。与对照组相比，BACE1和PS1水平仅在AD组升高，而BACE1和γ-分泌酶活性在MCI组和AD组均显著增强。最后，观察MCI和AD患者在血小板APP处理的几个标志物上的差异和相似之处。需要分析来自不同人群的更大样本集，以确定MCI或AD病理的存在特征，并在MCI阶段早期发现AD。
It has been suggested that mild cognitive impairment (MCI) patients deteriorate faster than the healthy elderly population and have an increased risk of developing dementia. Certain blood molecular biomarkers have been identified as prognostic markers in Alzheimer's disease (AD). The present study was aimed to assess the status of the platelet amyloid precursor protein (APP) metabolism in MCI and AD subjects and establish to what extent any variation could have a prognostic value suggestive of predictive AD in MCI patients. Thirty-four subjects diagnosed with MCI and 45 subjects with AD were compared to 28 healthy elderly individuals for assessing for protein levels of APP, beta-APP cleaving enzyme 1 (BACE1), presenilin 1 (PS1) and a disintegrin and metalloproteinase-10 (ADAM-10) by western blot, and for the enzyme activities of BACE1 and gamma-secretase by using specific fluorogenic substrates, in samples of platelets. A similar pattern in the healthy elderly and MCI patients was found for BACE1 and PS1 levels. A reduction of APP levels in MCI and AD patients compared with healthy elderly individuals was found. Augmented levels of ADAM-10 in both MCI and AD were displayed in comparison with age-matched control subjects. The ratio ADAM-10/BACE1 was higher for the MCI group versus AD group. Whereas BACE1 and PS1 levels were only increased in AD regarding to controls, BACE1 and gamma-secretase activities augmented significantly in both MCI and AD groups. Finally, differences and similarities between MCI and AD patients were observed in several markers of platelet APP processing. Larger sample sets from diverse populations need to be analyzed to define a signature for the presence of MCI or AD pathology and to early detect AD at the MCI stage.