CRISPR-Powered Aptasensor for Diagnostics of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia, characterized by the accumulation of amyloid beta (Aβ) peptides in the brain. Here, we present a simple, rapid, and affordable CRISPR-powered aptasensor for the quantitative detection of Aβ40 and Aβ42 biomarkers in cerebrospinal fluid (CSF) samples, enabling early and accurate diagnostics of AD patients. The aptasensor couples the high specificity of aptamers for Aβ biomarkers with CRISPR-Cas12a-based fluorescence detection. The CRISPR-powered aptasensor enables us to detect Aβ40 and Aβ42 in CSF samples within 60 min, achieving a detection sensitivity of 1 pg/mL and 0.1 pg/mL, respectively. To validate its clinical utility, we quantitatively detected Aβ40 and Aβ42 biomarkers in clinical CSF samples. Furthermore, by combining CSF Aβ42 levels with the c(Aβ42)/c(Aβ40) ratio, we achieved an accurate diagnostic classification of AD patients and healthy individuals, showing superior performance over the conventional ELISA method. We believe that our innovative aptasensor approach holds promise for the early diagnostic classification of AD patients.