Nanosensor-Driven Detection of Neuron-Derived Exosomal Aβ42 with Graphene Electrolyte-Gated Transistor for Alzheimer’s Disease Diagnosis

• Published in: Analytical chemistry (Washington) Vol. 95; no. 13; pp. 5719 - 5728
• Main Authors: Li, Jiahao, Ni, Wei, Jin, Dan, Yu, Yi, Xiao, Meng-Meng, Zhang, Zhi-Yong, Zhang, Guo-Jun
• Format: Journal Article
• Language: English
• Published: Washington American Chemical Society 04.04.2023
• Subjects: Alzheimer's disease; analytical chemistry; Antifouling substances; Background noise; Biomarkers; Biosensors; Blood; blood serum; Chemistry; dementia; Dementia disorders; detection limit; Diagnosis; Diagnostic systems; Differential diagnosis; early diagnosis; Electrolytes; Enzyme-linked immunosorbent assay; Forging; Graphene; Nanosensors; Neurodegenerative diseases; Nondestructive testing; Semiconductor devices; Transistors; Vascular dementia
• ISSN: 0003-2700; 1520-6882; 1520-6882
• DOI: 10.1021/acs.analchem.2c05751

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 Aβ42 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 Aβ42 (NDE-Aβ42), 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 Aβ42 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-Aβ42, which can outclass that of serum Aβ42. The developed electronic assay demonstrates, for the first time, nanosensor-driven NDE-Aβ42 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-Aβ42 biosensor defines a robust approach for blood-based confident AD ascertain.