High-Performance Plasma Biomarker Panel for Alzheimer’s Disease Screening Using a Femtomolar-Level Label-Free Biosensing System

Alzheimer's disease (AD) is the most common cause of dementia in older people. However, diagnosing AD through noncognitive methods, such as invasive cerebrospinal fluid sampling or radioactive positron emission tomography, has limited applications. Herein, the femtomolar levels of AD biomarkers amyloid β 40 (Aβ40), amyloid β 42 (Aβ42), phosphorylated tau 181 (P-tau181), phosphorylated tau 217 (P-tau217), and neurofilament light chain (NfL) were determined in human plasma in multicenter clinical cohorts using an ultrasensitive graphene field-effect transistor sensor. A machine-learning algorithm was also used to assemble these plasma biomarkers and optimize their performance in discriminating individual stages of Alzheimer's dementia progression. The "composite-info" biomarker panel, which combines these biomarkers and clinical information, considerably improved the staging performance in AD progression. It achieved an area under the curve of >0.94 in the receiver operator characteristic (ROC) curve. In addition, the panel demonstrated an advantage in the individual-based stage assessment compared with that of the Mini-Mental State Examination/Montreal Cognitive Assessment and nuclear magnetic resonance imaging. This study provides a composite biomarker panel for the screening and early diagnosis of AD using a rapid detection system.