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

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.