In this work, a highly sensitive label-free immunosensor for detection of the main biomarker of Alzheimer's disease (AD), amyloid beta 1-42 (A␤ (1-42)), is presented. A gold electrode was modified with a mercaptopropionic acid (MPA) self-assembled monolayer, electrodeposited gold nanoparticles (AuNPs) and a monoclonal antibody mAb DE2B4 to recognize A␤; all the relevant experimental variables were optimized. Antibodies were functionalized through chemical modification (thiolation) to promote the antibody immobilization on the AuNPs surface with proper orientation which enabled the direct detection of A␤(1-42). Scanning electron microscopy, square-wave voltammetry and electrochemical impedance spectroscopy were used to characterize the construction of the biosensor. Using the proposed immunosensor, A␤(1-42) was specifically detected within the linear range of 10-1000 pg mL −1 with a 5.2 pg mL −1 and 17.4 pg mL −1 detection and quantification limit, respectively; recovery values for the tested spiking levels ranged from 90.3 to 93.6%. The immunosensor enables rapid, accurate, precise, reproducible and highly sensitive detection (14.6% reduction mL pg −1) of A␤ with low-cost and opens the possibilities for diagnostic ex vivo applications and research-based in vivo studies. .

Alzheimer’s disease (AD) is an incurable and highly debilitating condition characterized by the progressive degeneration and/or death of nerve cells, which leads to manifestation of disabilities in cognitive functioning. In recent years, the development of biosensors for determination of AD’s main biomarkers has made remarkable progress, particularly based on the tremendous advances in nanoscience and nanotechnology. The unique and outstanding properties of nanomaterials (such as graphene, carbon nanotubes, gold, silver and magnetic nanoparticles, polymers and quantum dots) have been contributing to enhance the electrochemical and optical behavior of transducers while offering a suitable matrix for the immobilization of biological recognition elements. Therefore, optical and electrochemical immuno- and DNA-biosensors with higher sensitivity, selectivity and longer stability have been reported. Nevertheless, strategies based on the detection of multiple analytes still need to be improved, as they will play a crucial role in minimizing misdiagnosis. This review aims to provide insights into the conjugation of nanomaterials with different transducers highlighting their crucial role in the construction of biosensors for detection of AD main biomarkers.

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Alzheimer's disease is a neurodegenerative pathology characterized by extracellular accumulation of senile plaques, intracellular appearance of neurofibrillary tangles and neuronal loss. The amyloid beta-peptide soluble oligomers may have an important role in the Alzheimer's disease pathology. The current diagnostic procedures of Alzheimer's disease are difficult and are made in an advanced stage. Immunosensors can serve as novel diagnostic tools for Alzheimer's disease. The combination of highly selective immunosensors with electrochemical techniques offers the possibility to perform sensitive analyses. In this work, an electrochemical immunosensor for IJ-amyloid peptide detection in biological fluids will be presented.