Cerebrospinal Fluid Levels of Amyloid Beta 1-43 in Patients with Amnestic Mild Cognitive Impairment or Early Alzheimer's Disease: A 2-Year Follow-Up Study
Cerebrospinal Fluid Levels of Amyloid Beta 1-43 in Patients with Amnestic Mild Cognitive Impairment or Early Alzheimer's Disease: A 2-Year Follow-Up Study
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DOI：
10.3389/fnagi.2016.00030
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发表时间：
2016-03-01
影响因子：
4.8
通讯作者：
White, Linda R.
中科院分区：
文献类型：
--
作者：
Lauridsen, Camilla;Sando, Sigrid B.;White, Linda R.
前言：目前迫切需要能够可靠预测阿尔茨海默病(AD)发病的生物标志物。虽然脑脊液淀粉样β1-42(Aβ42)、总tau和磷酸化tau可用于补充AD的临床诊断，但作为AD的前驱阶段的遗忘性轻度认知损害(AMCI)是异质性的。生物标记物应该能够确定哪些急性心肌梗死患者有最大的AD风险。组织学和动物模型研究表明，淀粉样蛋白β1-43(Aβ43)早期聚集，并可能在AD的病理过程中发挥作用。在一项为期两年的aMCI和早期AD的纵向研究中，我们检测了脑脊液Aβ43的水平。材料和方法：收集基线、一年和两年后AD患者(n=19)和aMCI患者(n=42)的脑脊液。在这两年的研究中，21人进展到AD，而21人没有。对照组(n=32)仅在基线时进行腰椎穿刺术。用ELISA分析脑脊液中Aβ43、Aβ42和总tau。结果：基线时，可以用脑脊液Aβ43、脑脊液Aβ42和总tau的比值来区分所有三组患者。脑脊液Aβ43，而不是Aβ42，可以将在2年随访中进展为AD的aMCI患者与那些没有进展到AD的患者区分开来。与脑脊液总tau/Aβ42比值相比，脑脊液总tau/Aβ43比值在受试者工作特征曲线下的面积略大，但明显更大。在AD组中，脑脊液Aβ43水平从基线水平下降到2年，而不是Aβ42水平。讨论与结论：与对照组相比，在确诊为急性心肌梗死或AD时，脑脊液Aβ43水平显著降低，这种变化一定发生在临床前阶段。由于我们的结果表明，脑脊液Aβ43比脑脊液Aβ42更好地区分aMCI患者亚组，它可能被证明是识别aMCI患者AD风险最高的有用的附加生物标志物。
Introduction: Biomarkers that will reliably predict the onset of Alzheimer's disease (AD) are urgently needed. Although cerebrospinal fluid (CSF) amyloid beta 1-42 (A beta 42), total tau, and phosphorylated tau can be used to complement the clinical diagnosis of AD, amnestic mild cognitive impairment (aMCI), the prodromal phase of AD, is heterogeneous. Biomarkers should be able to determine which patients with aMCI are at greatest risk of AD. Histological studies and animal models indicate that amyloid beta 1-43 (A beta 43) aggregates early, and may play a role in the pathological process of AD. We have examined levels of CSF A beta 43 in a 2-year longitudinal study of aMCI and early AD.Materials and Methods: Cerebrospinal fluid was collected at baseline, and after one and 2 years from patients with AD (n = 19), and patients with aMCI (n = 42). Of these, 21 progressed to AD during the 2 years of study, whereas 21 did not. Controls (n = 32) were lumbar punctured at baseline only. CSF analyses of A beta 43, A beta 42, and total tau were carried out with ELISA.Results: At baseline, CSF A beta 43, CSF A beta 42 and ratios with total tau could be used to separate controls from all three patient groups. CSF A beta 43, but not A beta 42, could separate patients with aMCI who progressed to AD during the 2 years of follow-up, from those that did not. The CSF total tau/A beta 43 ratio had a slightly but significantly larger area under the receiver operating characteristic curve when compared to the CSF total tau/A beta 42 ratio. CSF A beta 43 levels, but not A beta 42 levels, decreased from baseline to 2 years in the AD group.Discussion and Conclusion: CSF A beta 43 was demonstrated to be significantly reduced in patients already by the time that aMCI or AD was diagnosed, compared to controls, and this change must have occurred during the preclinical period. Since our results suggested that CSF A beta 43 distinguishes between subgroups of patients with aMCI better than CSF A beta 42, it may prove to be a useful additional biomarker for identifying aMCI patients at greatest risk of AD.