▎ 摘　　要

Blood-based tests have sparked tremendous attention in noninvasive 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 Afi42 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 Afi42 (NDE-Afi42), 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-SY5Yderived exosomal Afi42 was also achieved with highly conformable enzyme linked immunosorbent assay results. Importantly, the clinical analysis for 27 subjects revealed the immense diagnostic value of NDEAfi42, which can outclass that of serum Afi42. The developed electronic assay demonstrates, for the first time, nanosensor-driven NDE-Afi42 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-Afi42 biosensor defines a robust approach for blood-based confident AD ascertain.