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.

Abstract

BackgroundCurrent methods to quantify blood biomarkers for Alzheimer's disease (AD) are expensive and are not widely available.ObjectiveTo develop a low-cost, sensitive, and accurate multiplex assay to quantify Aβ₄₀, Aβ₄₂, p181Tau, p217Tau, NfL, and GFAP biomarkers in plasma and serum based on a widely available technology.MethodsWe used commercial antibodies to Aβ₄₀, Aβ₄₂, 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.ResultsThe 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/Aβ₄₂ (r = 0.57), p217Tau/Aβ₄₂ (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.ConclusionsThe 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.