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Biosensors for Earlier Diagnosis of Alzheimer’s Disease
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Biosensors for Earlier Diagnosis of Alzheimer’s Disease

A special issue of Biosensors (ISSN 2079-6374). This special issue belongs to the section "Biosensors and Healthcare".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 16251

Special Issue Editors

Prof. Dr. Lúcio Angnes

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Guest Editor
Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes 748, São Paulo 05508-000, Brazil
Interests: eletroanalytical chemistry; electrode modifications; biosensors
Special Issues, Collections and Topics in MDPI journals
Dr. Hossein Heli

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Guest Editor
Nanomedicine and Nanobiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Interests: biosensors; nanomedicine; electrocatalysis
Special Issues, Collections and Topics in MDPI journals
Dr. Masoud Negahdary

E-Mail Website
Guest Editor
Institute of Chemistry, University of São Paulo (USP), São Paulo, Brazil
Interests: electrochemical biosensors; nanomaterials; biomarkers; moleculrs diagnosis of diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Alzheimer's disease is a type of brain dysfunction and an illness that destroys the brain's gray matter, in which the patient’s mental abilities gradually decline, and the patient suffers from a type of memory disorder that has a gradual onset and progression. According to the World Health Organization (WHO), Alzheimer's disease is currently the leading cause of disability for the elderly worldwide. This disease is one of the major health problems with a significant incidence through aging. The use of new technologies has simplified the diagnosis of various diseases. The diagnosis and prognosis of Alzheimer's disease using biosensors have recently received great attention. As modern diagnostic tools, biosensors will play a vital role in laboratory and traditional diagnoses of biomarkers related to this irreversible neurodegenerative disease. Amyloid-β (Aβ) and tau proteins are the main biomarkers for diagnosing this disease. In this Special Issue, the latest research and review efforts in the field of biosensors for the diagnosis of Alzheimer's disease will be considered. The sensitive and selective detection of specific biomarkers of Alzheimer's disease will be considered, and the use of new technologies such as nanomaterials, novel polymers, and innovative platforms in the design of these biosensors can provide valuable miniature tools for future molecular diagnoses of this critical disease.

Prof. Dr. Lúcio Angnes
Prof. Dr. Hossein Heli
Dr. Masoud Negahdary
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biosensors is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Alzheimer’s disease
  • biomarkers
  • bioanalysis
  • biosensors
  • early diagnosis

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Published Papers (5 papers)

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Research

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11 pages, 3158 KiB  
Communication
Vertical Graphene-Based Printed Electrochemical Biosensor for Simultaneous Detection of Four Alzheimer’s Disease Blood Biomarkers
by Mifang Li, Yu Zeng, Zhen Huang, Lingyan Zhang and Yibiao Liu
Biosensors 2023, 13(8), 758; https://doi.org/10.3390/bios13080758 - 25 Jul 2023
Cited by 5 | Viewed by 2071
Abstract
Early detection and timely intervention play a vital role in the effective management of Alzheimer’s disease. Currently, the diagnostic accuracy for Alzheimer’s disease based on a single blood biomarker is relatively low, and the combined use of multiple blood biomarkers can greatly improve [...] Read more.
Early detection and timely intervention play a vital role in the effective management of Alzheimer’s disease. Currently, the diagnostic accuracy for Alzheimer’s disease based on a single blood biomarker is relatively low, and the combined use of multiple blood biomarkers can greatly improve diagnostic accuracy. Herein, we report a printed electrochemical biosensor based on vertical graphene (VG) modified with gold nanoparticles (VG@nanoAu) for the simultaneous detection of four Alzheimer’s disease blood biomarkers. The printed electrochemical electrode array was constructed by laser etching and inkjet printing. Then gold nanoparticles were modified onto the working electrode surface via electrodeposition to further improve the sensitivity of the sensor. In addition, the entire printed electrochemical sensing system incorporates an electrochemical micro-workstation and a smartphone. The customized electrochemical micro-workstation incorporates four electro-chemical control chips, enabling the sensor to simultaneously analyze four biomarkers. Consequently, the printed electrochemical sensing system exhibits excellent analytical performance due to the large surface area, biocompatibility, and good conductivity of VG@nanoAu. The detection limit of the sensing system for Aβ40, Aβ42, T-tau, and P-tau181 was 0.072, 0.089, 0.071, and 0.051 pg/mL, respectively, which meets the detection requirements of Alzheimer’s disease blood biomarkers. The printed electrochemical sensing system also exhibits good specificity and stability. This work has great value and promising prospects for early Alzheimer’s disease diagnosis using blood biomarkers. Full article
(This article belongs to the Special Issue Biosensors for Earlier Diagnosis of Alzheimer’s Disease)
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13 pages, 2248 KiB  
Article
Ultrasensitive Determination of Glial-Fibrillary-Acidic-Protein (GFAP) in Human Serum-Matrix with a Label-Free Impedimetric Immunosensor
by Goksu Ozcelikay, Fariba Mollarasouli, Mehmet Altay Unal, Kıvılcım Gucuyener and Sibel A. Ozkan
Biosensors 2022, 12(12), 1165; https://doi.org/10.3390/bios12121165 - 14 Dec 2022
Cited by 5 | Viewed by 3331
Abstract
In this work, immobilizing anti-GFAP antibodies via covalent attachment onto L-cysteine/gold nanoparticles that were modified with screen-printed carbon electrodes (Anti-GFAP/L-cys/AuNps/SPCE) resulted in the development of a sensitive label-free impedance immunosensor for the detection of Glial Fibrillary Acidic Protein (GFAP). The immunosensor’s stepwise construction [...] Read more.
In this work, immobilizing anti-GFAP antibodies via covalent attachment onto L-cysteine/gold nanoparticles that were modified with screen-printed carbon electrodes (Anti-GFAP/L-cys/AuNps/SPCE) resulted in the development of a sensitive label-free impedance immunosensor for the detection of Glial Fibrillary Acidic Protein (GFAP). The immunosensor’s stepwise construction was studied using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). L-cysteine was chosen as the linker between GFAP antibodies and Au NPs/SPCE because it enables the guided and stable immobilization of GFAP antibodies, thus resulting in increased immunosensor sensitivity. As a redox probe, 5 mM of [Fe(CN)6]3−/4− was used to measure the electron–transfer resistance (Ret), which was raised by the binding of antigens to the immobilized anti-GFAP on the surface of the modified electrode. A linear correlation between Rct and GFAP concentration was achieved under optimum conditions in the range of 1.0–1000.0 pg/mL, with an extraordinarily low detection limit of 51.0 fg/mL. The suggested immunosensor was successfully used to detect the presence of GFAP in human blood serum samples, yielding good findings. As a result, the proposed platform may be utilized to monitor central nervous system injuries. Full article
(This article belongs to the Special Issue Biosensors for Earlier Diagnosis of Alzheimer’s Disease)
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11 pages, 1752 KiB  
Article
Applications of Immunomagnetic Reduction Technology as a Biosensor in Therapeutic Evaluation of Chinese Herbal Medicine in Tauopathy Alleviation of an AD Drosophila Model
by Ming-Tsan Su, Chen-Wen Lu, Wen-Jhen Wu, Yong-Sin Jheng, Shieh-Yueh Yang, Wu-Chang Chuang, Ming-Chung Lee and Chung-Hsin Wu
Biosensors 2022, 12(10), 883; https://doi.org/10.3390/bios12100883 - 17 Oct 2022
Cited by 2 | Viewed by 2408
Abstract
Alzheimer’s disease (AD) is the most common form of dementia. The most convincing biomarkers in the blood for AD are currently β-amyloid (Aβ) and Tau protein because amyloid plaques and neurofibrillary tangles are pathological hallmarks in the brains of patients with AD. The [...] Read more.
Alzheimer’s disease (AD) is the most common form of dementia. The most convincing biomarkers in the blood for AD are currently β-amyloid (Aβ) and Tau protein because amyloid plaques and neurofibrillary tangles are pathological hallmarks in the brains of patients with AD. The development of assay technologies in diagnosing early-stage AD is very important. The study of human AD subjects is hindered by ethical and technical limitations. Thus, many studies have therefore turned to AD animal models, such as Drosophila melanogaster, to explore AD pathology. However, AD biomarkers such as Aβ and p-Tau protein in Drosophilamelanogaster occur at extremely low levels and are difficult to detect precisely. In this study, we applied the immunomagnetic reduction (IMR) technology of nanoparticles for the detection of p-Tau expressions in hTauR406W flies, an AD Drosophila model. Furthermore, we used IMR technology as a biosensor in the therapeutic evaluation of Chinese herbal medicines in hTauR406W flies with Tau-induced toxicity. To uncover the pathogenic pathway and identify therapeutic interventions of Chinese herbal medicines in Tau-induced toxicity, we modeled tauopathy in the notum of hTauR406W flies. Our IMR data showed that the selected Chinese herbal medicines can significantly reduce p-Tau expressions in hTauR406W flies. Using evidence of notal bristle quantification and Western blotting analysis, we confirmed the validity of the IMR data. Thus, we suggest that IMR can serve as a new tool for measuring tauopathy and therapeutic evaluation of Chinese herbal medicine in an AD Drosophila model. Full article
(This article belongs to the Special Issue Biosensors for Earlier Diagnosis of Alzheimer’s Disease)
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12 pages, 1936 KiB  
Article
In-Depth Characterization of Endo-Lysosomal Aβ in Intact Neurons
by Alec K. McKendell, Mei C. Q. Houser, Shane P. C. Mitchell, Michael S. Wolfe, Oksana Berezovska and Masato Maesako
Biosensors 2022, 12(8), 663; https://doi.org/10.3390/bios12080663 - 20 Aug 2022
Cited by 7 | Viewed by 2651
Abstract
Amyloid-beta (Aβ) peptides are produced within neurons. Some peptides are released into the brain parenchyma, while others are retained inside the neurons. However, the detection of intracellular Aβ remains a challenge since antibodies against Aβ capture Aβ and its precursor proteins (i.e., APP [...] Read more.
Amyloid-beta (Aβ) peptides are produced within neurons. Some peptides are released into the brain parenchyma, while others are retained inside the neurons. However, the detection of intracellular Aβ remains a challenge since antibodies against Aβ capture Aβ and its precursor proteins (i.e., APP and C99). To overcome this drawback, we recently developed 1) the C99 720-670 biosensor for recording γ-secretase activity and 2) a unique multiplexed immunostaining platform that enables the selective detection of intracellular Aβ with subcellular resolution. Using these new assays, we showed that C99 is predominantly processed by γ-secretase in late endosomes and lysosomes, and intracellular Aβ is enriched in the same subcellular loci in intact neurons. However, the detailed properties of Aβ in the acidic compartments remain unclear. Here, we report using fluorescent lifetime imaging microscopy (FLIM) that intracellular Aβ includes both long Aβ intermediates bound to γ-secretase and short peptides dissociated from the protease complex. Surprisingly, our results also suggest that the dissociated Aβ is bound to the glycoproteins on the inner membrane of lysosomes. Furthermore, we show striking cell-to-cell heterogeneity in intracellular Aβ levels in primary neurons and APP transgenic mouse brains. These findings provide a basis for the further investigation of the role(s) of intracellular Aβ and its relevance to Alzheimer’s disease (AD). Full article
(This article belongs to the Special Issue Biosensors for Earlier Diagnosis of Alzheimer’s Disease)
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Review

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28 pages, 2938 KiB  
Review
Electrochemical Immunosensors Developed for Amyloid-Beta and Tau Proteins, Leading Biomarkers of Alzheimer’s Disease
by Abhinav Sharma, Lúcio Angnes, Naghmeh Sattarahmady, Masoud Negahdary and Hossein Heli
Biosensors 2023, 13(7), 742; https://doi.org/10.3390/bios13070742 - 17 Jul 2023
Cited by 16 | Viewed by 4619
Abstract
Alzheimer’s disease (AD) is the most common neurological disease and a serious cause of dementia, which constitutes a threat to human health. The clinical evidence has found that extracellular amyloid-beta peptides (Aβ), phosphorylated tau (p-tau), and intracellular tau proteins, which are derived from [...] Read more.
Alzheimer’s disease (AD) is the most common neurological disease and a serious cause of dementia, which constitutes a threat to human health. The clinical evidence has found that extracellular amyloid-beta peptides (Aβ), phosphorylated tau (p-tau), and intracellular tau proteins, which are derived from the amyloid precursor protein (APP), are the leading biomarkers for accurate and early diagnosis of AD due to their central role in disease pathology, their correlation with disease progression, their diagnostic value, and their implications for therapeutic interventions. Their detection and monitoring contribute significantly to understanding AD and advancing clinical care. Available diagnostic techniques, including magnetic resonance imaging (MRI) and positron emission tomography (PET), are mainly used to validate AD diagnosis. However, these methods are expensive, yield results that are difficult to interpret, and have common side effects such as headaches, nausea, and vomiting. Therefore, researchers have focused on developing cost-effective, portable, and point-of-care alternative diagnostic devices to detect specific biomarkers in cerebrospinal fluid (CSF) and other biofluids. In this review, we summarized the recent progress in developing electrochemical immunosensors for detecting AD biomarkers (Aβ and p-tau protein) and their subtypes (AβO, Aβ(1-40), Aβ(1-42), t-tau, cleaved-tau (c-tau), p-tau181, p-tau231, p-tau381, and p-tau441). We also evaluated the key characteristics and electrochemical performance of developed immunosensing platforms, including signal interfaces, nanomaterials or other signal amplifiers, biofunctionalization methods, and even primary electrochemical sensing performances (i.e., sensitivity, linear detection range, the limit of detection (LOD), and clinical application). Full article
(This article belongs to the Special Issue Biosensors for Earlier Diagnosis of Alzheimer’s Disease)
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