Advancing Early Diagnosis of Alzheimer’s Disease: A Paper-Based Aptasensor for Detecting A β (1-42) and p-tau181 from Plasma Using CdTe Quantum Dots

ABSTRACT Alzheimer’s Disease (AD), characterized by a gradual onset and a lack of exact therapeutic interventions, underscores the imperative for the development of uncomplicated and cost-effective biosensors capable of detecting its biomarkers. This necessity arises in anticipation of a projected surge in the incidence of AD. Quantum dots (QDs) represent the promising new generation of luminophores owing to their size, composition, and surface-dependent tunable photoluminescence (PL) and photochemical stability. In this study, a paper-based QD aptasensor for the early detection of AD by targeting amyloid beta (A β -42) and p-tau181 proteins using Förster Resonance Energy Transfer (FRET) is developed. The sensor employs a Whatman paper with six sensing wells, integrating hydrophobic and hydrophilic regions, hydrophobic parts created through wax. Blood samples are placed in the inlet, dispersing into six sensing wells containing QD-aptamer-AuNP complexes. Target proteins induce conformational changes in aptamers, leading to fluorescence quenching in CdTe QDs. Two wells target p-tau181, two target amyloid beta-42, and two serve as references. Fluorescence emission spectra from each well are recorded, showing a linear correlation between fluorescence quenching and protein concentration. Values from each pair of wells are then averaged, and the average values from the pairs targeting (A β -42) and p-tau181 are compared to the average value of the reference wells. This paper-based aptasensor holds promise for early diagnosis of Alzheimer’s Disease and opens the avenue of personalized medicine for the diagnosis of Alzheimer’s.