关键词: Alzheimer’s disease Early diagnosis Lumipulse Plasma biomarkers Screening Validation

Mesh : Humans Alzheimer Disease / diagnostic imaging tau Proteins / cerebrospinal fluid Amyloid beta-Peptides / cerebrospinal fluid Peptide Fragments / cerebrospinal fluid Biomarkers / cerebrospinal fluid Amyloid

来  源:   DOI:10.1186/s13195-023-01319-1   PDF(Pubmed)

Abstract:
The arrival of new disease-modifying treatments for Alzheimer\'s disease (AD) requires the identification of subjects at risk in a simple, inexpensive, and non-invasive way. With tools allowing an adequate screening, it would be possible to optimize the use of these treatments. Plasma markers of AD are very promising, but it is necessary to prove that alterations in their levels are related to alterations in gold standard markers such as cerebrospinal fluid or PET imaging. With this research, we want to evaluate the performance of plasma Aβ40, Aβ42, and p-tau181 to detect the pathological changes in CSF using the automated Lumipulse platform.
Both plasma and CSF Aβ40, Aβ42, and p-tau181 have been evaluated in a group of 208 cognitively unimpaired subjects with a 30.3% of ApoE4 carriers. We have correlated plasma and CSF values of each biomarker. Then, we have also assessed the differences in plasma marker values according to amyloid status (A - / +), AD status (considering AD + subjects to those A + plus Tau +), and ATN group defined by CSF. Finally, ROC curves have been performed, and the area under the curve has been measured using amyloid status and AD status as an outcome and different combinations of plasma markers as predictors.
Aβ42, amyloid ratio, p-tau181, and p-tau181/Aβ42 ratio correlated significantly between plasma and CSF. For these markers, the levels were significantly different in the A + / - , AD + / - , and ATN groups. Amyloid ratio predicts amyloid and AD pathology in CSF with an AUC of 0.89.
Plasma biomarkers of AD using the automated Lumipulse platform show good diagnostic performance in detecting Alzheimer\'s pathology in cognitively unimpaired subjects.
摘要:
背景:阿尔茨海默病(AD)新的疾病修饰治疗方法的到来需要在一个简单的,便宜,和非侵入性的方式。有了允许适当筛查的工具,有可能优化这些治疗方法的使用。AD的血浆标志物非常有前途,但有必要证明其水平的改变与脑脊液或PET成像等黄金标准标志物的改变有关。通过这项研究,我们希望使用自动Lumipulse平台评估血浆Aβ40,Aβ42和p-tau181检测CSF病理变化的性能.
方法:已在208名认知未受损的受试者中评估了血浆和CSFAβ40,Aβ42和p-tau181,其中ApoE4携带者占30.3%。我们已经将每种生物标志物的血浆和CSF值相关联。然后,我们还根据淀粉样蛋白状态(A-/+)评估了血浆标志物值的差异,AD状态(考虑AD+科目为A++Tau+),和由CSF定义的ATN组。最后,ROC曲线已经完成,并且已经使用淀粉样蛋白状态和AD状态作为结果以及血浆标志物的不同组合作为预测因子来测量曲线下面积。
结果:Aβ42,淀粉样蛋白比率,p-tau181和p-tau181/Aβ42比率在血浆和CSF之间显着相关。对于这些标记,水平在A+/-中显著不同,AD+/-,和ATN组。淀粉样蛋白比率以0.89的AUC预测CSF中的淀粉样蛋白和AD病理学。
结论:使用自动Lumipulse平台的AD血浆生物标志物在认知未受损受试者中检测阿尔茨海默病病理学方面显示出良好的诊断性能。
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