Abstract：
BACKGROUND: The analysis of the core biomarkers of Alzheimer\'s Disease (AD) in the cerebrospinal fluid (CSF) is recommended in the clinical units where it is available. Because of the absence of universal validated values, the determination of specific cut-off points for each center and its population is recommended. The main objective of the CORCOBIA study was to determine the cut-off points of core AD CSF biomarkers for several centers (Parc de Salut Mar, Barcelona and Hospital General de Granollers), which work with the same reference laboratory (Laboratori de Referència de Catalunya).
METHODS: Prospective study including cognitively unimpaired individuals (CU, n = 42), subjects with amnestic mild cognitive impairment (aMCI, n = 35) and patients with dementia due to Alzheimer\'s Disease (AD, n = 48), in whom clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture to analyse amyloid beta peptides (Aβ42, Aβ40), total tau (tTau) and phosphorylated Tau (pTau181) using the Lumipulse G600II (Fujirebio) was performed. The values of sensitivity (SE), specificity (SP), predictive values and area under the curve (AUC) were calculated, determining the cut-off point according to the Youden index by comparing the CU and AD groups.
RESULTS: The resulting cut-offs and their AUC were the following: Aβ42 750 pg/mL (AUC 0.809); Aβ42/Aβ40 0.062 (AUC 0.78); pTau181 69.85 pg/mL (AUC 0.81); tTau 522.0 pg/mL (AUC 0.79); Aβ42/tTau 1.76 (AUC 0.86); Aβ42/pTau181 10.25 (AUC 0.86).
CONCLUSIONS: The determination of cut-off points of core AD CSF biomarkers for the participating centers allows a better diagnostic accuracy. The ratio CSF Aβ42/pTau181 shows the highest AUC and better balance between sensitivity and specificity.
METHODS: Prospective study including cognitively unimpaired individuals (CU, n = 42), subjects with amnestic mild cognitive impairment (aMCI, n = 35) and patients with dementia due to Alzheimer\'s Disease (AD, n = 48), in whom clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture to analyse amyloid beta peptides (Aβ42, Aβ40), total tau (tTau) and phosphorylated Tau (pTau181) using the Lumipulse G600II (Fujirebio) was performed. The values of sensitivity (SE), specificity (SP), predictive values and area under the curve (AUC) were calculated, determining the cut-off point according to the Youden index by comparing the CU and AD groups.
RESULTS: The resulting cut-offs and their AUC were the following: Aβ42 750 pg/mL (AUC 0.809); Aβ42/Aβ40 0.062 (AUC 0.78); pTau181 69.85 pg/mL (AUC 0.81); tTau 522.0 pg/mL (AUC 0.79); Aβ42/tTau 1.76 (AUC 0.86); Aβ42/pTau181 10.25 (AUC 0.86).
CONCLUSIONS: The determination of cut-off points of core AD CSF biomarkers for the participating centers allows a better diagnostic accuracy. The ratio CSF Aβ42/pTau181 shows the highest AUC and better balance between sensitivity and specificity.
摘要：
背景：临床单位推荐对脑脊液（CSF）中阿尔茨海默病（AD）的核心生物标志物进行分析。由于缺乏普遍的验证值，建议确定每个中心及其人口的具体截止点。CORCOBIA研究的主要目的是确定几个中心的核心ADCSF生物标志物的临界点(ParcdeSalutMar，BarcelonaandHospitalGeneraldeGranollers),与相同的参考实验室（加泰罗尼亚实验室）一起工作。
方法：包括认知健康受试者的前瞻性研究(HC，n=42),患有遗忘型轻度认知障碍的受试者（aMCI，n=35）和因阿尔茨海默病引起的痴呆患者（AD，n=48),其中临床和神经心理学评估，神经影像学,APOE基因分型和腰椎穿刺分析淀粉样β肽（Aβ42，Aβ40），使用LumipulseG600II（Fujirebio）进行总tau（tTau）和磷酸化Tau（pTau181）。灵敏度(Se)的值，特异性(Sp),计算预测值和曲线下面积（AUC），通过比较HC和AD组，根据Youden指数确定临界点。
结果：所得截止值及其AUC如下：Aβ42750pg/ml（AUC0.809）；Aβ42/Aβ400.062（AUC0.78）；pTau18169.85pg/ml（AUC0.81）；tTau522.0pg/ml（AUC0.79）；Aβ42/Tau1.76（10.C）
结论：确定参与中心的核心ADCSF生物标志物的截止点可以获得更好的诊断准确性。CSFAβ42/pTau181的比率显示出最高的AUC以及灵敏度和特异性之间的更好平衡。
方法：包括认知健康受试者的前瞻性研究(HC，n=42),患有遗忘型轻度认知障碍的受试者（aMCI，n=35）和因阿尔茨海默病引起的痴呆患者（AD，n=48),其中临床和神经心理学评估，神经影像学,APOE基因分型和腰椎穿刺分析淀粉样β肽（Aβ42，Aβ40），使用LumipulseG600II（Fujirebio）进行总tau（tTau）和磷酸化Tau（pTau181）。灵敏度(Se)的值，特异性(Sp),计算预测值和曲线下面积（AUC），通过比较HC和AD组，根据Youden指数确定临界点。
结果：所得截止值及其AUC如下：Aβ42750pg/ml（AUC0.809）；Aβ42/Aβ400.062（AUC0.78）；pTau18169.85pg/ml（AUC0.81）；tTau522.0pg/ml（AUC0.79）；Aβ42/Tau1.76（10.C）
结论：确定参与中心的核心ADCSF生物标志物的截止点可以获得更好的诊断准确性。CSFAβ42/pTau181的比率显示出最高的AUC以及灵敏度和特异性之间的更好平衡。
