High precision and cost-effective multiplex quantification of amyloid-β40, amyloid-β42, p181Tau, p217Tau, neurofilament light chain, and glial fibrillary acidic protein from plasma and serum

胶质纤维酸性蛋白 多路复用 脑脊液 接收机工作特性 医学 病理 化学 分子生物学 免疫学 内科学 生物 生物信息学 免疫组织化学
作者
Farshad Alishahi,Christopher R. Beam,Margaret Gatz,Lon S. Schneider,Daniel A. Nation,Hussein N. Yassine,Hillard Kaplan,Suchita Ganesan,Ioannis Pappas,Deborah Winders Davis,Ebrahim Zandi
出处
期刊:Journal of Alzheimer's Disease [IOS Press]
标识
DOI:10.1177/13872877251340999
摘要

Background Current methods to quantify blood biomarkers for Alzheimer's disease (AD) are expensive and are not widely available. Objective To develop a low-cost, sensitive, and accurate multiplex assay to quantify Aβ 40 , Aβ 42 , p181Tau, p217Tau, NfL, and GFAP biomarkers in plasma and serum based on a widely available technology. Methods We used commercial antibodies to Aβ 40 , Aβ 42 , p181Tau, p217Tau, NfL, and GFAP, and xMAP Luminex technology, and developed the multiplex 5ADCSI to quantify these biomarkers from plasma and serum. The utility of 5ADCSI was tested in matched cerebrospinal fluid (CSF) and plasma or serum of a cohort of cognitively normal (CN: n = 35), with mild cognitive impairment (MCI: n = 17), and with AD (n = 11) individuals. Results The 5ADCSI demonstrated high specificity and sensitivity, with excellent precision. In clinical samples, moderate to strong correlation is observed between CSF and plasma or serum for Aβ 42/40 ( r = 0.78 ), p181Tau/Aβ 42 ( r = 0.57 ), p217Tau/Aβ 42 ( r = 0.72 ), p181Tau ( r = 0.59 ), p217Tau ( r = 0.75 ), and GFAP ( r = 0.59 ). The AUC of receiver-operator characteristic curve for differentiating CN from AD for plasma/serum and CSF are 0.75, and 0.80 for Aβ 42/40 , 0.95, 0.91 for p217Tau, 0.76, 0.81 for p181Tau, and 0.73 and 0.78for GFAP, respectively. Conclusions The 5ADCSI assay is highly specific, sensitive, and accurate. The wide availability of the base technology of 5ADCSI is an advantage over other similar methods and would allow cost-effective large-scale studies for validation of blood biomarkers for early diagnosis of AD.

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