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Alzheimer's disease (AD) is closely related to neurodegeneration, leading to dementia and cognitive impairment, especially in people aged > 65 years old. The detection of biomarkers plays a pivotal role in the diagnosis and treatment of AD, particularly at the onset stage. Field-effect transistor (FET)-based sensors are emerging devices that have drawn considerable attention due to their crucial ability to recognize various biomarkers at ultra-low concentrations. Thus, FET is broadly manipulated for AD biomarker detection. In this review, an overview of typical FET features and their operational mechanisms is described in detail. In addition, a summary of AD biomarker detection and the applicability of FET biosensors in this research field are outlined and discussed. Furthermore, the trends and future prospects of FET devices in AD diagnostic applications are also discussed. [ABSTRACT FROM AUTHOR]

Alzheimer's disease has taken the spotlight as a neurodegenerative disease which has caused crucial issues to both society and the economy. Specifically, aging populations in developed countries face an increasingly serious problem due to the increasing budget for patient care and an inadequate labor force, and therefore a solution is urgently needed. Recently, diverse techniques for the detection of Alzheimer's biomarkers have been researched and developed to support early diagnosis and treatment. Among them, electrochemical biosensors and electrode modification proved their effectiveness in the detection of the Aβ biomarker at appropriately low concentrations for practice and point-of-care application. This review discusses the production and detection ability of amyloid beta, an Alzheimer's biomarker, by electrochemical biosensors with SAM support for antibody conjugation. In addition, future perspectives on SAM for the improvement of electrochemical biosensors are also proposed and discussed. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), a heterogeneous pathological process representing the most common causes of dementia worldwide, has required early and accurate diagnostic tools. Neuropathological hallmarks of AD involve the aberrant accumulation of Amyloid beta (Aβ) into Amyloid plaques and hyperphosphorylated Tau into neurofibrillary tangles, occurring long before the onset of brain dysfunction. Areas covered:Considering the significance of Aβ and Tau in AD pathogenesis, these proteins have been adopted as core biomarkers of AD, and their quantification has provided precise diagnostic information to develop next-generation AD therapeutic approaches. However, conventional diagnostic methods may not suffice to achieve clinical criteria that are acceptable for proper diagnosis and treatment. The advantages of nanomaterial-based biosensors including facile miniaturization, mass fabrication, ultra-sensitivity, make them useful to be promising tools to measure Aβ and Tau simultaneously for accurate validation of low-abundance yet potentially informative biomarkers of AD.. The study has identified the potential application of advanced biosensors as standardized clinical diagnostic tools for AD, evolving the way for new and efficient AD control with minimum economic and social burden. After clinical trial, nanobiosensors for measuring Aβ and Tau simultaneously possess innovative diagnosis of AD to provide significant contributions to primary Alzheimer's care intervention. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel DNA-incorporated activated carbon nanocomposite was developed. • Phosphate-mediated H 2 O 2 decomposition was studied using the DFT/B3LYP/6–31++G** set. • The developed metal-free sensor detects H 2 O 2 at a nanomolar concentration (2.5 nM). • DNA@AC was employed for H 2 O 2 analysis on Raw 264.7 cells and milk samples. • The sensor displays anti-interference properties, long-term storage stability and repeatability. Hydrogen peroxide (H 2 O 2) is one of the most important reactive oxygen species (ROS). Increased endogenous H 2 O 2 levels indicate oxidative stress and could be a potential marker of many diseases, including Alzheimer's, cardiovascular diseases, and diabetes. However, consuming H 2 O 2- incorporated food has adverse effects on humans and is a serious health concern. We used salmon testes DNA with bio-inspired activated carbon (AC) as an electrocatalyst for developing a novel H 2 O 2 sensor. The phosphate backbone of DNA contains negatively charged oxygen groups that specifically attract protons from H 2 O 2 reduction. We observed a linearity range of 0.01–250.0 μM in the H 2 O 2 reduction peak current with a detection limit of 2.5 and 45.7 nM for chronoamperometric and differential pulse voltammetric studies. High biocompatibility of the sensor was achieved by the DNA, facilitating endogenous H 2 O 2 detection. Moreover, this non-enzymatic sensor could also help in the rapid screening of H 2 O 2 -contaminated foods. [ABSTRACT FROM AUTHOR]

The pathology of Alzheimer's disease (AD), the most common cause of dementia, is considered to be mainly driven by two major hallmarks (tau and amyloid beta). It is highly desirable to develop an affordable medicinal diagnostic that can be utilized worldwide for the early diagnosis of AD. Hence, p-tau231 was selected as a specific target, which appears both in AD serum and cerebrospinal fluid, for the development of a sensing platform for the diagnosis of AD. To the best of our knowledge, these are the first aptamer-mediated biosensors that rely on sensitive fluorescent and colorimetric aptasensors for the rapid monitoring of p-tau231. The nitrogen-doped carbon dot-based turn-on fluorescent aptasensor could rapidly analyze p-tau231 down to 3.64 ng/mL within 40 min, and the colorimetric Cu-enhanced-Au aptablot displayed high sensitivity at 4.71 pg/mL through a digital camera, with visibility to the naked eye down to 8 ng/mL p-tau231 within 140 min. Owing to their advantages, which include affordability, rapidity, high sensitivity, and dependence on complicated instruments, these aptamer-based biosensors offer significant potential for the early diagnosis of AD worldwide. [ABSTRACT FROM AUTHOR]

The development of an electrochemical biosensor for the detection of phosphorylated-tau threonine 231 (p-tau231), a biomarker of Alzheimer's disease (AD), has yet to be achieved. Therefore, in this study, we developed a simple, small size, cheap, and sensitive electrochemical biosensor based on an interdigitated wave-shaped electrode via an activated self-assembled monolayer to preserve a specific anti–p-tau231 antibody (IWE/SAM/EDC-NHS/anti–p-tau231). Detection of p-tau231 in human serum (HS) using the biosensor was undertaken using electrochemical impedance spectroscopy (EIS). The change in charge-transfer resistance (Rct) in the EIS analysis of the biosensor indicated the detection of p-tau231 in HS within a wide linear range of detection (10−4–101 ng mL−1), and a low limit of detection (140 pg mL−1). This lower limit is less than the detection level of p-tau231 in cerebrospinal fluid (CSF) (700 pg mL−1) of AD patients and the level of CSF p-tau231 of patients with mild cognitive impairment (501 pg mL−1), demonstrating the possibility of using the biosensor in detection of p-tau231 at early stage AD. A high binding affinity and low dissociation constant (Kd) between anti–p-tau231 and p-tau231 in HS was demonstrated by using a biosensor and Kd was 7.6 pM, demonstrating the high specific detection of p-tau231 by the biosensor. The good selectivity of the biosensor for the detection of p-tau231 with differential analytes was also examined in this study. [ABSTRACT FROM AUTHOR]

The early diagnosis of Alzheimer's disease (AD) remains a challenge for medical scientists worldwide, leading to a number of research efforts that focus on biosensor development for AD biomarkers. However, the application of these complicated biosensors is limited in medical diagnosis, due to the difficulties in robust sensing platform development, high costs, and the necessity for technical professionals. We successfully developed a robust straightforward manufacturing process for the fabrication of multi-chamber paper devices using the wax printing method and exploited it to detect amyloid beta 42 oligomers (AβO42, a significant biomarker of AD) using copper-enhanced gold nanoprobe colorimetric immunoblotting. Small hydrophilic reaction chambers could concentrate the target sample to the desired size to improve the sensing performance. The copper-enhanced gold nanoprobe immunoblot using the designed multi-chamber platform exhibited a highly sensitive performance with a limit of detection of 320 pg/mL by the naked eye and 23.7 pg/mL by a smartphone camera. This process from sensing manufacture to sensing conduction is simple to perform whenever medical technicians require time- and cost-savings, without complicated instruments or the need for technical professionals, making it feasible to serve as a diagnostic tool worldwide for the early monitoring of AD and scalable devices for the sensing application of various biomarkers in clinical settings. [ABSTRACT FROM AUTHOR]

Aggregation of amyloid-β (aβ) peptides into toxic oligomers, fibrils, and plaques is central in the molecular pathogenesis of Alzheimer's disease (AD) and is the primary focus of AD diagnostics. Disaggregation or elimination of toxic aβ aggregates in patients is important for delaying the progression of neurodegenerative disorders in AD. Recently, 4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid (EPPS) was introduced as a chemical agent that binds with toxic aβ aggregates and transforms them into monomers to reduce the negative effects of aβ aggregates in the brain. However, the mechanism of aβ disaggregation by EPPS has not yet been completely clarified. In this study, an electrochemical impedimetric immunosensor for aβ diagnostics was developed by immobilizing a specific anti-amyloid-β (aβ) antibody onto a self-assembled monolayer functionalized with a new interdigitated chain-shaped electrode (anti-aβ/SAM/ICE). To investigate the ability of EPPS in recognizing AD by extricating aβ aggregation, commercially available aβ aggregates (aβagg) were used. Electrochemical impedance spectroscopy was used to probe the changes in charge transfer resistance (Rct) of the immunosensor after the specific binding of biosensor with aβagg. The subsequent incubation of the aβagg complex with a specific concentration of EPPS at different time intervals divulged AD progression. The decline in the Rct of the immunosensor started at 10 min of EPPS incubation and continued to decrease gradually from 20 min, indicating that the accumulation of aβagg on the surface of the anti-aβ/SAM/ICE sensor has been extricated. Here, the kinetic disaggregation rate k value of aβagg was found to be 0.038. This innovative study using electrochemical measurement to investigate the mechanism of aβagg disaggregation by EPPS could provide a new perspective in monitoring the disaggregation periods of aβagg from oligomeric to monomeric form, and then support for the prediction and handling AD symptoms at different stages after treatment by a drug, EPPS. [ABSTRACT FROM AUTHOR]

Emerging nanomaterials providing benefits in sensitivity, specificity and cost-effectiveness are being widely investigated for biosensors in the application of Alzheimer's disease (AD) diagnosis. Core biomarkers amyloid-beta (Aβ) and Tau have been considered as key neuropathological hallmarks of AD. However, they did not sufficiently reflect clinical severity and therapeutic response, proving the difficulty of the Aβ- and Tau-targeting therapies in clinical trials. In recent years, there has still been a shortage of sensors for non-Aβ-Tau pathophysiological biomarkers that serve as advanced reporters for the early diagnosis of AD, predict AD progression, and monitor the treatment response. Nanomaterial-based sensors measuring multiple non-Aβ-Tau biomarkers could improve the capacity of AD progression characterization and supervised treatment, facilitating the comprehensive management of AD. This is the first review to principally represent current nanobiosensors for non-Aβ-Tau biomarker and that strategically deliberates future perspectives on the merit of non-Aβ-Tau biomarkers, in combination with Aβ and Tau, for the accurate diagnosis and prognosis of AD. [ABSTRACT FROM AUTHOR]

Plasma phosphorylated-tau threonine 181 (p-tau181) is a promising biomarker for predicting Alzheimer's disease (AD) and mild cognitive impairment (MCI), which is the symptomatic pre-dementia stage of AD. To date, there are limitations in the current diagnosis and classification of the two stages of MCI and AD in clinical practice remain a dilemma. In this study, we aimed to discriminate and diagnose patients with MCI, AD, and healthy participants based on the accurate, label-free, and ultrasensitive detection of p-tau181 levels in human clinical plasma samples using our developed electrochemical impedance-based biosensor, which allows to detect p-tau181 at a very low concentration of 0.92 fg mL−1. Human plasma samples were collected from 20 patients with AD, 20 patients with MCI, and 20 individuals with healthy control. The change in charge-transfer resistance of the developed impedance-based biosensor caused by capturing p-tau181 in plasma samples was recorded to evaluate the determination of plasma p-tau181 levels in human clinical samples for discrimination and diagnosis of AD, MCI, and healthy control individuals, respectively. Receiver operating characteristic (ROC) curve, a standard analysis to judge the clinically diagnostic capability of our biosensor platform based on the estimated levels of plasma p-tau181, resulted a sensitivity of 95%, a specificity of 85%, the area under the ROC curve (AUC) value of 0.94 of the accuracy for discriminating AD patients from healthy controls; a sensitivity of 70%, a specificity of 70%, the AUC of 0.75 to discriminate MCI patients from healthy controls. Statistical analysis (one-way analysis of variance (ANOVA)) was used to compare the estimated plasma p-tau181 levels in clinical samples, indicated significantly higher for AD patients with healthy controls (***p ≤ 0.001), AD with MCI patients (***p ≤ 0.001), and MCI patients with healthy controls (*p ≤ 0.05), respectively. In addition, we compared our sensor to the global cognitive function scales and discovered that it performed noticeably improvement in diagnosing the stages of AD. These results demonstrated the good application of our developed electrochemical impedance-based biosensor in the identification of clinical disease stages. Moreover, in this study, a small dissociation constant (K D) of 0.533 pM was first determined to evaluate the high binding affinity between the p-tau181 biomarker and its antibody, providing a reference parameter for future studies of the p-tau181 biomarker and AD. [Display omitted] • An ultrasensitive electrochemical impedance biosensor for detection of p-tau181 biomarker in clinical plasma is first reported. • The first determination of the dissociation constant (K D) for p-tau181 biomarker is achieved. • Plasma p-tau181 levels are proven to discriminate and diagnose 40 patients with clinical AD stages& 20 healthy individuals. • The good diagnostics capability of the biosensor for identification of clinical dementia stages is achieved. [ABSTRACT FROM AUTHOR]

In this paper, we developed a new ultrasensitive capacitance sensor for detection of amyloid beta 1-40 (aβ40) protein (one of Alzheimer's disease core biomarkers) in human serum based on the high supramolecular recognition of the β-cyclodextrin/reduced graphene oxide (β-CD/RGO) nanohybrid toward the anti-aβ40 antibody molecule. The sensor was established by immobilizing specific anti-aβ40 antibody onto the β-CD/RGO nanohybrid functionalized on indium tin oxide micro-disk electrode (anti-aβ40/β-CD/RGO/ITO). Detection of aβ40 in the human serum (HS) using the sensor anti-aβ40/β-CD/RGO/ITO is carried out by capacitance measurement without a redox probe to prevent protein denaturation, serving as a convenient strategy for point-of-care diagnosis. In comparison with other studies, the sensor shows a very low limit of detection of 0.69 fg mL−1 in HS, demonstrating its ability for the ultrasensitive detection of aβ40. Using this sensor, the dissociation constant K D of the binding interaction between anti-aβ40 and aβ40 in HS is found to be 2.9 × 10−7 nM, indicating the high binding affinity of antibody–antigen and the suitability of the anti-aβ40/β-CD/RGO/ITO sensor for aβ40 protein detection. The good selectivity of the anti-aβ40/β-CD/RGO/ITO sensor in the presence of differential analytes was also performed in this paper. [Display omitted] • First development a capacitance sensor for ultrasensitive detection of aβ40 using supramolecular recognition. • The sensor (anti-aβ40/β-CD/RGO/ITO) was established through host–guest inclusion complex. • Avoiding the denaturation of protein during the detection using the capacitance sensor. • A very low LOD (0.69 fg mL-1) and low K D (2.9×10-7 nM) of aβ40 in human serum. [ABSTRACT FROM AUTHOR]

In this study, we developed a small size, low cost, highly sensitive electrochemical biosensor with a low limit of detection by immobilizing specific anti-amyloid-β (aβ) antibody onto a self-assembled monolayer functionalized interdigitated chain-shaped electrode (anti-aβ/EDC–NHS/SAM/ICE). The anti-aβ/EDC–NHS/SAM/ICE specifically detects aβ 1–42 peptide (a peptide 1–42 amino acids long), which is one of main biomarkers of Alzheimer's disease in human serum (HS). Electrochemical impedance spectroscopy (EIS) was used to characterize the impedance change of the anti-aβ/EDC–NHS/SAM/ICE biosensor for aβ 1–42 detection, which provided a wide linear range of detection from 10−3–103 ng mL−1, and a low limit of detection of aβ in HS (100 pg mL−1) much lower than the limit of detection of CSF aβ 1–42 (∼500 pg mL−1), and other biosensors. Therefore, the developed biosensor is sensitive enough to be used for the diagnosis of early stage Alzheimer's disease. • The specific anti-aβ antibody functionalized ICE electrode is designed to improve electric field homogeneity. • Label-free and real-time detection of aβ 1–42 using electrochemical impedance spectroscopy. • A low LOD (100 pg mL−1) with a linear detection range of 10−3–103 ng mL−1 in human serum is reported. [ABSTRACT FROM AUTHOR]