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血小板中的淀粉样前体蛋白:一种用于散发性阿尔茨海默病诊断的外周标志物。

Amyloid precursor protein in platelets: a peripheral marker for the diagnosis of sporadic AD.

作者信息

Padovani A, Pastorino L, Borroni B, Colciaghi F, Rozzini L, Monastero R, Perez J, Pettenati C, Mussi M, Parrinello G, Cottini E, Lenzi G L, Trabucchi M, Cattabeni F, Di Luca M

机构信息

Dipt. Scienze Mediche e Chirurgiche, Unità di Neurologia, Università degli Studi di Brescia, Italy.

出版信息

Neurology. 2001 Dec 26;57(12):2243-8. doi: 10.1212/wnl.57.12.2243.

DOI:10.1212/wnl.57.12.2243
PMID:11756604
Abstract

BACKGROUND

An altered pattern of amyloid precursor protein (APP) forms consisting in a reduced ratio between the upper (130 kDa) and the lower (106 to 110 kDa) immunoreactivity bands has been described in platelets of patients with AD.

OBJECTIVE

To evaluate the sensitivity and the specificity of platelet APP forms' ratio (APPr) as a marker for AD.

METHODS

Eighty-five patients with probable AD and 95 control subjects (CON), including healthy individuals and neurologic patients, entered the study. Platelet APPr was evaluated by means of Western Blot analysis and immunostaining in the whole platelet homogenate, and calculated by the ratio between the optical density (OD) of the upper (130 kDa) and the lower (106 to 110 kDa) APP immunoreactive bands.

RESULTS

Mean APPr levels were decreased in AD patients (mean OD +/- SD = 0.35 +/- 0.18) compared with the CON group (mean OD +/- SD = 0.92 +/- 0.38) (DF 1, 178, p < 0.0001). Accuracy levels measured by Receiver Operating Curve analysis showed that a cut-off level of 0.57 resulted in a sensitivity of 88.2% and a specificity of 89.4%, with an area under the curve of 0.945. APPr levels were significantly associated with disease severity (mild AD versus moderate AD: p < 0.0001; moderate AD versus severe AD: p < 0.05).

CONCLUSION

Platelet APPr allowed to differentiate AD from normal aging and other dementing disorders with high sensitivity and specificity. These findings suggest that platelet APPr may be of help as an adjunctive diagnostic tool in clinical practice.

摘要

背景

在阿尔茨海默病(AD)患者的血小板中,已发现淀粉样前体蛋白(APP)形式的改变模式,即上部(130 kDa)与下部(106至110 kDa)免疫反应条带之间的比例降低。

目的

评估血小板APP形式比例(APPr)作为AD标志物的敏感性和特异性。

方法

85例可能患有AD的患者和95名对照受试者(CON),包括健康个体和神经系统疾病患者,进入本研究。通过蛋白质免疫印迹分析和全血小板匀浆中的免疫染色评估血小板APPr,并通过上部(130 kDa)与下部(106至110 kDa)APP免疫反应条带的光密度(OD)之比计算得出。

结果

与CON组相比,AD患者的平均APPr水平降低(平均OD +/- SD = 0.35 +/- 0.18)(CON组平均OD +/- SD = 0.92 +/- 0.38)(自由度1, 178,p < 0.0001)。通过受试者工作特征曲线分析测得的准确度水平显示,临界值为0.57时,敏感性为88.2%,特异性为89.4%,曲线下面积为0.945。APPr水平与疾病严重程度显著相关(轻度AD与中度AD:p < 0.0001;中度AD与重度AD:p < 0.05)。

结论

血小板APPr能够以高敏感性和特异性将AD与正常衰老及其他痴呆性疾病区分开来。这些发现表明,血小板APPr可能有助于在临床实践中作为辅助诊断工具。

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