Clinically accurate diagnosis of Alzheimer\u2019s disease via multiplexed sensing of core biomarkers in human plasma

Kayoung Kim,Min-Ji Kim,Su Yeong Kim,Steve Park,Chan Beum Park,Da Won Kim

doi:10.1038/s41467-019-13901-z

Kayoung Kim, Min-Ji Kim + Show 4 more

Open Access

https://doi.org/10.1038/s41467-019-13901-z

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Abstract

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder, affecting one in ten people aged over 65 years. Despite the severity of the disease, early diagnosis of AD is still challenging due to the low accuracy or high cost of neuropsychological tests and neuroimaging. Here we report clinically accurate and ultrasensitive detection of multiple AD core biomarkers (t-tau, p-tau181, Aβ42, and Aβ40) in human plasma using densely aligned carbon nanotubes (CNTs). The closely packed and unidirectionally aligned CNT sensor array exhibits high precision, sensitivity, and accuracy, evidenced by a low coefficient of variation (<6%), a femtomolar-level limit of detection, and a high degree of recovery (>93.0%). By measuring the levels of t-tau/Aβ42, p-tau181/Aβ42, and Aβ42/Aβ40 in clinical blood samples, the sensor array successfully discriminates the clinically diagnosed AD patients from healthy controls with an average sensitivity of 90.0%, a selectivity of 90.0%, and an average accuracy of 88.6%.

Highlights

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder, affecting one in ten people aged over 65 years
We prepared densely aligned carbon nanotubes (CNTs) films using the Langmuir–Blodgett (LB) transfer method, which involves compressing the CNTs at the water–air interface and their subsequent transfer onto a silicon substrate (Supplementary Fig. 1)
The addition of target AD biomarkers to the sensor arrays reduced the source-to-drain currents at the negative gate voltage, leaving the positive gate voltage region unaffected. These results indicate that target AD biomarkers captured by the corresponding recognition elements acted as scattering centers on CNTs23 and eventually decreased the array’s conductance

Summary

Introduction

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder, affecting one in ten people aged over 65 years. We report clinically accurate and ultrasensitive detection of multiple AD core biomarkers (t-tau, p-tau[181], Aβ42, and Aβ40) in human plasma using densely aligned carbon nanotubes (CNTs). By measuring the levels of t-tau/Aβ42, p-tau181/Aβ42, and Aβ42/Aβ40 in clinical blood samples, the sensor array successfully discriminates the clinically diagnosed AD patients from healthy controls with an average sensitivity of 90.0%, a selectivity of 90.0%, and an average accuracy of 88.6%. Clinical diagnosis of AD relies largely on neuropsychological tests and neuroimaging, but the low accuracy of cognitive assessments and the high cost of brain imaging leave a large number of AD patients diagnosed late or not at all[3]. We substantiate that the densely aligned CNT sensor array can discriminate clinically diagnosed AD patients from normal controls by estimating the levels of composite AD biomarkers (t-tau/Aβ42, p-tau/Aβ42, and Aβ42/Aβ40) in human plasma

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