Label-free paper-based electrochemical aptasensor with tunable selectivity for assessing neurotransmitter imbalance in Alzheimer’s disease

A paper-based electrochemical aptasensor (PEA) is reported for the simultaneous detection of extracellular dopamine (DA) and serotonin (SE) in human brain samples, enabling the assessment of neurotransmitter imbalances associated with Alzheimer's disease (AD). The PEA integrates a dual-selectivity strategy that combines aptamer-mediated molecular recognition with potential-resolved electrochemical neurotransmitters discrimination, allowing reliable differentiation between healthy and AD-diagnosed left prefrontal cortex tissues based on altered dopaminergic and serotonergic levels. Thiolated aptamers immobilized onto gold nanoparticles (AuNPs) at the paper electrode interface provide selective neurotransmitter biorecognition, while the distinct oxidation potentials of DA (+ 0.10 V) and SE (+ 0.25 V vs. Ag/AgCl) enable their label-free, simultaneous quantification on a single disposable electrode. The PEA read biologically meaningful concentration shifts across a clinically relevant dynamic range, spanning levels characteristic of healthy tissue to those observed in advanced pathological stages. The PEA approach highlights its potential for liquid biopsy-oriented neurochemical monitoring and supports its application in multiplexed biosensing within organ-on-a-chip systems, enabling early diagnostic strategies for neurodegenerative diseases.