Neurofilament light chain protein (NfL) has emerged as a valuable biomarker in various neurodegenerative diseases (NDs). Initially, NfL detection relied on invasive cerebrospinal fluid (CSF) sampling. Although the concentration of NfL in serum is low, it shows a positive correlation with that in CSF. However, current methods for serum NfL detection suffer from limitations such as inadequate sensitivity and operational complexity. This study developed a novel assay leveraging antibody-conjugated magnetic nanospheres for target capture and fluorescent nanospheres for quantification, significantly enhancing the sensitivity, accuracy, and stability for serum NfL detection. Under optimal conditions, the method exhibited a linear relationship between fluorescence intensity and NfL concentration across 0.005–10 ng/mL with a detection limit of 1.4 pg/mL. Spiked recovery experiments performed in 5-fold diluted human serum samples demonstrated 95.4–103.2% recovery, confirming high accuracy and clinical utility. Overall, the established method may offer a promising new approach for the auxiliary diagnosis of NDs.
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.
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