Nanosensor-Driven Detection of Neuron-Derived Exosomal Aβ<sub>42</sub> with Graphene Electrolyte-Gated Transistor for Alzheimer’s Disease Diagnosis
Jiahao Li, Wei Ni, Dan Jin, Yi Yu, Mengmeng Xiao, Zhiyong Zhang, Guojun Zhang
Abstract
Blood-based tests have sparked tremendous attention in non-invasive early diagnosis of Alzheimer’s disease (AD), a most prevalent neurodegenerative malady worldwide. Despite significant progress in the methodologies for detecting AD core biomarkers such as Aβ 42 from serum/plasma, there remains cautious optimism going forward due to its controversial diagnostic value and disease relevance. Here, a graphene electrolyte-gated transistor biosensor is reported for the detection of serum neuron-derived exosomal Aβ 42 (NDE-Aβ 42 ), which is an emerging, compelling trove of blood biomarker for AD. Assisted by the antifouling strategy with the dual-blocking process, the noise against complex biological background was considerably reduced, forging an impressive sensitivity gain with a limit of detection of 447 ag/mL. An accurate detection of SH-SY5Y-derived exosomal Aβ 42 was also achieved with highly conformable enzyme-linked immunosorbent assay results. Importantly, the clinical analysis for 27 subjects revealed the immense diagnostic value of NDE-Aβ 42, which can outclass that of serum Aβ 42 . The developed electronic assay demonstrates, for the first time, nanosensor-driven NDE-Aβ 42 detection, which enables a reliable discrimination of AD patients from non-AD individuals and even the differential diagnosis between AD and vascular dementia patients, with an accuracy of 100% and a Youden index of 1. This NDE-Aβ 42 biosensor defines a robust approach for blood-based confident AD ascertain.