CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios: better diagnostic markers of Alzheimer disease.
CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios: better diagnostic markers of Alzheimer disease.
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DOI：
10.1002/acn3.274
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发表时间：
2016-03
影响因子：
5.3
通讯作者：
Hansson O
中科院分区：
文献类型：
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作者：
Janelidze S;Zetterberg H;Mattsson N;Palmqvist S;Vanderstichele H;Lindberg O;van Westen D;Stomrud E;Minthon L;Blennow K;Swedish BioFINDER study group;Hansson O
在广泛应用于临床之前，必须提高脑脊液（CSF）生物标志物对阿尔茨海默病（AD）诊断的准确性。本研究旨在确定与单独CSF Aβ42相比，CSF Aβ42/Aβ40和Aβ42/Aβ38比值是否是痴呆前期和痴呆阶段AD的更好诊断生物标志物。该研究包括3个不同队列（n = 1182），评估了Aβ42、Aβ40和Aβ38的CSF水平。使用三种不同的免疫测定法（Euroimmun、Meso Scale Discovery、Quanterix）定量CSF Aβ。作为参考标准，我们使用淀粉样蛋白（18 F-flutemetetamine）正电子发射断层扫描（PET）成像（n = 215）或临床诊断（n = 967）的良好表征的患者。当在主观认知下降和轻度认知功能障碍的病例中使用三种不同的免疫测定时，CSF Aβ42/Aβ40和Aβ42/Aβ38比值是比CSF Aβ42显著更好的异常淀粉样蛋白PET的预测因子。较低的Aβ42、Aβ42/Aβ40和Aβ42/Aβ38比值与磁共振成像测量的海马体积较小相关，但与Aβ40和Aβ38无关。然而，较低的Aβ38、Aβ40和Aβ42（而非比值）与非AD特异性皮质下变化相关，即侧脑室和白色病变较大。此外，当区分AD与路易体痴呆或帕金森病痴呆和皮质下血管性痴呆时，Aβ42/Aβ40和Aβ42/Aβ38比值显示出比Aβ42更高的准确性，其中所有Aβ（包括Aβ42）均降低。CSF Aβ42/Aβ40和Aβ42/Aβ38比值在检测前驱AD的脑淀粉样蛋白沉积和区分AD痴呆与非AD痴呆方面显著优于CSF Aβ42。该比值更好地反映了AD型病理学，而CSF Aβ42的下降也与非AD皮质下病理学相关。这些结果强烈表明，在AD的临床检查中应使用比值而不是CSF Aβ42。
The diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) must be improved before widespread clinical use. This study aimed to determine whether CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios are better diagnostic biomarkers of AD during both predementia and dementia stages in comparison to CSF Aβ42 alone. The study comprised three different cohorts (n = 1182) in whom CSF levels of Aβ42, Aβ40, and Aβ38 were assessed. CSF Aβs were quantified using three different immunoassays (Euroimmun, Meso Scale Discovery, Quanterix). As reference standard, we used either amyloid (18F‐flutemetamol) positron emission tomography (PET) imaging (n = 215) or clinical diagnosis (n = 967) of well‐characterized patients. When using three different immunoassays in cases with subjective cognitive decline and mild cognitive impairment, the CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios were significantly better predictors of abnormal amyloid PET than CSF Aβ42. Lower Aβ42, Aβ42/Aβ40, and Aβ42/Aβ38 ratios, but not Aβ40 and Aβ38, correlated with smaller hippocampal volumes measured by magnetic resonance imaging. However, lower Aβ38, Aβ40, and Aβ42, but not the ratios, correlated with non‐AD‐specific subcortical changes, that is, larger lateral ventricles and white matter lesions. Further, the Aβ42/Aβ40 and Aβ42/Aβ38 ratios showed increased accuracy compared to Aβ42 when distinguishing AD from dementia with Lewy bodies or Parkinson's disease dementia and subcortical vascular dementia, where all Aβs (including Aβ42) were decreased. The CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios are significantly better than CSF Aβ42 to detect brain amyloid deposition in prodromal AD and to differentiate AD dementia from non‐AD dementias. The ratios reflect AD‐type pathology better, whereas decline in CSF Aβ42 is also associated with non‐AD subcortical pathologies. These findings strongly suggest that the ratios rather than CSF Aβ42 should be used in the clinical work‐up of AD.