Diagnostic Accuracy of Cerebrospinal Fluid Amyloid-β Isoforms for Early and Differential Dementia Diagnosis
Diagnostic Accuracy of Cerebrospinal Fluid Amyloid-β Isoforms for Early and Differential Dementia Diagnosis
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DOI：
10.3233/jad-141986
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发表时间：
2015-01-01
影响因子：
4
通讯作者：
Engelborghs, Sebastiaan
中科院分区：
文献类型：
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作者：
Struyfs, Hanne;Van Broeck, Bianca;Engelborghs, Sebastiaan
背景资料：阿尔茨海默病（AD）和非AD患者之间的重叠脑脊液生物标志物（CSF）水平降低了AD核心CSF生物标志物的鉴别诊断准确性。目的：通过与AD CSF生物标志物A β（1-42）、T-tau和P-tau（181 P）的比较，确定A β亚型A β（1-37）、A β（1-38）和A β（1-40）的附加诊断价值。使用MSD检测技术，用原型多重测定法分析了来自AD所致痴呆患者（n = 50）、非AD痴呆患者（n = 50）、AD所致轻度认知障碍患者（n = 50）和非痴呆对照患者（n = 50）的CSF。非AD组包括额颞叶痴呆（FTD; n = 17）、路易体痴呆（DLB; n = 17）和血管性痴呆（n = 16）。A β（1-37）、A β（1-38）和A β（1-40）水平与AD所致痴呆的简易精神状态检查评分和病程相关。在大多数鉴别诊断情况下，A β（1-42）/A β（1-40）比值改善了A β（1-42）的诊断性能。A β（1-42）水平较低，载脂蛋白E β 4载体相比noncarriers.Conclusions：A β亚型有助于区分AD从FTD和DLB。A β亚型增加A β（1-42）的诊断性能。与A β（1-42）相反，A β亚型似乎与AD的疾病严重程度相关。将A β亚型添加到当前的生物标志物组中可以提高诊断准确性。
Background: Overlapping cerebrospinal fluid biomarkers (CSF) levels between Alzheimer's disease (AD) and non-AD patients decrease differential diagnostic accuracy of the AD core CSF biomarkers. Amyloid-beta (A beta) isoforms might improve the AD versus non-AD differential diagnosis.Objective: To determine the added diagnostic value of A beta isoforms, A beta(1-37), A beta(1-38), and A beta(1-40), as compared to the AD CSF biomarkers A beta(1-42), T-tau, and P-tau(181P).Methods: CSF from patients with dementia due to AD (n = 50), non-AD dementias (n = 50), mild cognitive impairment due to AD(n = 50) and non-demented controls (n = 50) was analyzed with a prototype multiplex assay using MSD detection technology. The non-AD group consisted of frontotemporal dementia (FTD; n = 17), dementia with Lewy bodies (DLB; n = 17), and vascular dementia (n = 16).Results: A beta(1-37) and A beta(1-38) increased accuracy to differentiate AD from FTD or DLB. A beta(1-37), A beta(1-38), and A beta(1-40) levels correlated with Mini-Mental State Examination scores and disease duration in dementia due to AD. The A beta(1-42)/A beta(1-40) ratio improved diagnostic performance of A beta(1-42) in most differential diagnostic situations. A beta(1-42) levels were lower in APOE epsilon 4 carriers compared to non-carriers.Conclusions: A beta isoforms help to differentiate AD from FTD and DLB. A beta isoforms increase diagnostic performance of A beta(1-42). In contrast to A beta(1-42), A beta isoforms seem to be correlated with disease severity in AD. Adding the A beta isoforms to the current biomarker panel could enhance diagnostic accuracy.