Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy
Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy
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DOI：
10.3233/jad-191254
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发表时间：
2020-01-01
影响因子：
4
通讯作者：
Werring, David J.
中科院分区：
文献类型：
--
作者：
Banerjee, Gargi;Ambler, Gareth;Werring, David J.
背景资料：关于散发性淀粉样β蛋白（A β）脑淀粉样血管病（CAA）患者脑脊液（CSF）生物标志物的研究资料有限。目的：确定CAA患者脑脊液中与神经退行性疾病相关的生物标志物的分布。我们对CSF标志物进行了详细的比较，比较了CAA患者、阿尔茨海默病（AD）患者和对照（CS）参与者，从CAA（BOCAA）研究中的生物标志物和结果以及专业认知障碍服务中招募。结果：我们包括10名CAA、20名AD和10名CS参与者（平均年龄分别为68.6岁、62.5岁和62.2岁）。在未校正的分析中，CAA患者具有独特的CSF生物标志物特征，A β（38）、A β（40）、A β（42）、sA β PP α和sA β PP β的中位浓度显著较低（p < 0.01）。CAA患者的神经丝光（NFL）水平高于CS组（p < 0.01），但CSF总tau、磷酸化tau、可溶性TREM 2（sTREM 2）或神经颗粒蛋白浓度没有显著差异。AD组总tau蛋白、磷酸化tau蛋白和神经颗粒蛋白含量高于CS组和CAA组。在年龄调整分析中，CAA组的A β（38），A β（40），A β（42）和sA β PP β仍存在差异。比较淀粉样蛋白PET阳性（n = 5）和阴性（n = 5）的CAA患者，PET阳性个体的（p < 0.05）CSF A β（42）的浓度，以及更高的总tau、磷酸化tau、NFL和神经颗粒蛋白浓度，与“AD样”特征一致。CAA具有特征性的生物标志物特征，提示淀粉样蛋白种类的全球性而非选择性积累;我们还根据淀粉样蛋白PET阳性提供了不同表型的证据。需要在更大的队列中进一步复制和验证这些初步研究结果。
Background: There is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-beta (A beta) cerebral amyloid angiopathy (CAA).Objective: To determine the profile of biomarkers relevant to neurodegenerative disease in the CSF of patients with CAA.Methods: We performed a detailed comparison of CSF markers, comparing patients with CAA, Alzheimer's disease (AD), and control (CS) participants, recruited from the Biomarkers and Outcomes in CAA (BOCAA) study, and a Specialist Cognitive Disorders Service.Results: We included 10 CAA, 20 AD, and 10 CS participants (mean age 68.6, 62.5, and 62.2 years, respectively). In unadjusted analyses, CAA patients had a distinctive CSF biomarker profile, with significantly lower (p < 0.01) median concentrations of A beta(38), A beta(40), A beta(42), sA beta PP alpha, and sA beta PP beta. CAA patients had higher levels of neurofilament light (NFL) than the CS group (p < 0.01), but there were no significant differences in CSF total tau, phospho-tau, soluble TREM2 (sTREM2), or neurogranin concentrations. AD patients had higher total tau, phospho-tau and neurogranin than CS and CAA groups. In age-adjusted analyses, differences for the CAA group remained for A beta(38), A beta(40), A beta(42), and sA beta PP beta. Comparing CAA patients with amyloid-PET positive (n = 5) and negative (n = 5) scans, PET positive individuals had lower (p < 0.05) concentrations of CSF A beta(42), and higher total tau, phospho-tau, NFL, and neurogranin concentrations, consistent with an "AD-like" profile.Conclusion: CAA has a characteristic biomarker profile, suggestive of a global, rather than selective, accumulation of amyloid species; we also provide evidence of different phenotypes according to amyloid-PET positivity. Further replication and validation of these preliminary findings in larger cohorts is needed.