Detection Of Alzheimer's Disease Biomarkers Research Articles

Gazing Beyond the Horizon: A Systematic Review Unveiling the Theranostic Potential of Quantum Dots in Alzheimer's Disease.

Alzheimer's disease (AD), a neurodegenerative disorder characterized by cognitive decline, poses a significant healthcare challenge worldwide. The accumulation of amyloid-beta (Aβ) plaques and hyperphosphorylated tau protein drives neuronal degeneration and neuroinflammation, perpetuating disease progression. Despite advancements in understanding the cellular and molecular mechanisms, treatment hurdles persist, emphasizing the need for innovative intervention strategies. Quantum dots (QDs) emerge as promising nanotechnological tools with unique photo-physical properties, offering advantages over conventional imaging modalities. This systematic review endeavors to elucidate the theranostic potential of QDs in AD by synthesizing preclinical and clinical evidence. A comprehensive search across electronic databases yielded 20 eligible studies investigating the diagnostic, therapeutic, or combined theranostic applications of various QDs in AD. The findings unveil the diverse roles of QDs, including inhibiting Aβ and tau aggregation, modulating amyloidogenesis pathways, restoring membrane fluidity, and enabling simultaneous detection of AD biomarkers. The review highlights the potential of QDs in targeting multiple pathological hallmarks, delivering therapeutic payloads across the blood-brain barrier, and facilitating real-time imaging and high-throughput screening. While promising, challenges such as biocompatibility, surface modifications, and clinical translation warrant further investigation. This systematic review provides a comprehensive synthesis of the theranostic potential of QDs in AD, paving the way for translational research and clinical implementation.

Ultrasensitive electrochemical detection of amyloid-beta oligomers using double amplification strategy by MXene substrate and covalent organic framework-based probe

Most of the existing electrochemical systems failed to achieve satisfactory results in early diagnosis of Alzheimer's disease (AD) owing to a deficiency of effective signal transduction. A new method for the electrochemical detection of AD biomarkers (amyloid-beta oligomers, Aβ1-42 oligomers) was developed based on a double amplification strategy. Titanium carbide (Ti3C2) MXene decorated by gold nanoparticles (Au-MXene) as the electrode substrate not only gave rise to the electrochemical response due to its paradoxical surface area and conspicuous charge mobility, but also provided vast numbers of binding sites for aptamers (Apt) of Aβ1-42 oligomers. Meanwhile, AuNPs were incorporated into covalent organic frameworks (COFs), which were further modified by Apt and electron mediator (toluidine blue, TB). The Apt/TB-Au@COFs composite was utilized as a label because of their improvement of the electron-hole separation efficiency and optimization of the charge-carrier utilization. The proposed electrochemical assay established highly efficient platform for the detection of Aβ1-42 oligomers with a linear range from 0.01 pg mL−1 to 180 pg mL−1 and an ultralow detection limit of 4.27 fg mL−1 (S/N = 3). This biosensing platform had potential applications in molecular diagnostics of AD serum samples.

Metal-organic frameworks: A promising option for the diagnosis and treatment of Alzheimer's disease.

Beta-amyloid (Aβ) peptide is one of the main characteristic biomarkers of Alzheimer's disease (AD). Previous clinical investigations have proposed that unusual concentrations of this biomarker in cerebrospinal fluid, blood, and brain tissue are closely associated with the AD progression. Therefore, the critical point of early diagnosis, prevention, and treatment of AD is to monitor the levels of Aβ. In view of the potential of metal-organic frameworks (MOFs) for diagnosing and treating the AD, much attention has been focused in recent years. This review discusses the latest advances in the applications of MOFs for the early diagnosis of AD via fluorescence and electrochemiluminescence (ECL) detection of AD biomarkers, fluorescence detection of the main metal ions in the brain (Zn2+, Cu2+, Mn2+, Fe3+, and Al3+) in addition to magnetic resonance imaging (MRI) of the Aβ plaques. The current challenges and future strategies for translating the in vitro applications of MOFs into in vivo diagnosis of the AD are discussed.

Ultrahigh Sensitive Detection of Tau Protein as Alzheimer's Biomarker via Microfluidics and Nanofunctionalized Optical Fiber Sensors

Alzheimer's disease (AD) is one of the most common neurodegenerative illnesses displaying the highest death rate in the elderly. However, the existing AD diagnostic system remains elusive due to lack of a technology that may ensure enough sensitivity and reproducibility, detection accuracy, and specificity. Herein, a straightforward approach is reported to realize lab‐on‐fiber (LoF) technology for AD biomarker detection based on a D‐shaped single‐mode fiber combined with nanometer‐scale metal‐oxide film. The proposed sensing system, which permits the generation of lossy‐mode resonance (LMR), remarkably increases the evanescent field of light guided through the fiber, and hence the fiber‐surrounding medium interaction. Moreover, such optical sensors are highly repeatable in results and can safely be embedded into a compact and stable microfluidic system. Herein, the specific detection of Tau protein (as one of the classical AD biomarkers that is highly correlated with AD progression) in a complex biofluid with a detection limit of 10−12 m and over a wide concentration range (10−3–10 μg mL−1) is successfully demonstrated. The proposed LoF biosensor is an appealing solution for rapid, sub‐microliter dose and highly sensitive detection of analytes at low concentrations, hereby having the potential toward early screening and personalized medicine in AD.

A Concise Overview of Biosensing Technologies for the Detection of Alzheimer's Disease Biomarkers.

Alzheimer's disease (AD) is a brain-linked pathophysiological condition with neuronal degeneration and cognition dysfunctions and other debilitations. Due to the growing prevalence of AD, there is a highly commended trend to accelerate and develop analytical technologies for easy, costeffective, and sensitive detection of AD biomarkers. Biosensors are commanding analytical devices that can conduct biological responses on transducers into measurable signals. This review focuses on up-todate developmets, contests, and tendencies regarding AD biosensing principally, with the emphasis on the exclusive possessions of nanomaterials. In the last decade, remarkable advancements have been achieved to the progression of biosensors, predominantly optical and electrochemical, for the detection of AD biomarkers. These analytical devices can assist the case finding and management of AD.

Highly sensitive surface-enhanced Raman scattering-based immunosensor incorporating half antibody-fragment for quantitative detection of Alzheimer's disease biomarker in blood

Blood-based detection of Alzheimer's disease (AD) biomarker has become a prominent method for diagnosis of AD which can replace the complex and invasive cerebrospinal fluid (CSF)-based diagnostic method. However, the application of blood AD biomarker in actual AD diagnosis is hampered by the extremely low concentration of biomarkers in blood, as well as the existence of interfering proteins. Therefore, it is essential to develop a sensitive and specific detection platform to achieve blood-based diagnosis of AD. Here, a surface-enhanced Raman scattering (SERS)-based sensor is developed for the quantitative determination of tau protein in the plasma of AD patients. To acquire femtomolar-level detection limit, this platform involves the use of half antibody fragment immobilized onto head-flocked gold nanopillar SERS substrates and SERS-nanotags. The small size of the half antibody fragment maximizes the effect of plasmon coupling, by reducing the distance between SERS substrates and SERS-nanotags. Also, the use of half antibody fragment improves the antigen recognition ability by immobilizing the antibody with high density and efficient orientation of the antibody. The sensor using these characteristics showed a low detection limit of 3.21 fM and a wide detection range (10 fM - 1 μM). The platform was also able to accurately quantify the tau protein in the clinical plasma sample and correctly distinguish the AD patient from the healthy control. The ultrasensitive and specific SERS immunoassay platform facilitates accurate and early detection of AD biomarkers and can serve as a valuable tool for simple point-of-care testing in clinical diagnosis.

Acoustofluidic multimodal diagnostic system for Alzheimer's disease

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative brain disorder that affects tens of millions of older adults worldwide and has significant economic and societal impacts. Despite its prevalence and severity, early diagnosis of AD remains a considerable challenge. Here we report an integrated acoustofluidics-based diagnostic system (ADx), which combines triple functions of acoustics, microfluidics, and orthogonal biosensors for clinically accurate, sensitive, and rapid detection of AD biomarkers from human plasma. We design and fabricate a surface acoustic wave-based acoustofluidic separation device to isolate and purify AD biomarkers to increase the signal-to-noise ratio. Multimodal biosensors within the integrated ADx are fabricated by in-situ patterning of the ZnO nanorod array and deposition of Ag nanoparticles onto the ZnO nanorods for surface-enhanced Raman scattering (SERS) and electrochemical immunosensors. We obtain the label-free detections of SERS and electrochemical immunoassay of clinical plasma samples from AD patients and healthy controls with high sensitivity and specificity. We believe that this efficient integration provides promising solutions for the early diagnosis of AD.

Novel Magnetic Beads with Improved Performance for Alzheimer's Disease Biomarker Detection

Novel Magnetic Beads with Improved Performance for Alzheimer's Disease Biomarker Detection

Bifunctional Au@Pt/Au core@shell Nanoparticles As Novel Electrocatalytic Tags in Immunosensing: Application for Alzheimer's Disease Biomarker Detection.

In this work, bifunctional core@shell Au@Pt/Au NPs are presented as novel tags for electrochemical immunosensing. Au@Pt/Au NPs were synthesized following a chemical route based on successive metal depositions and galvanic replacement reactions from the starting AuNPs. Au protuberances growth on the surface of Au@Pt NPs allowed their easy bioconjugation with antibodies, while the high catalytic Pt surface area was approached for their sensitive detection through the electrocatalyzed water oxidation reaction (WOR) at neutral pH. Moreover, the synergy between Au and Pt metals on the NP surface also lead to an increased catalytic activity, improving the sensitivity of the NP detection. Cyclic voltammetry and chronoamperometry were used for the evaluation of the Au@Pt/Au NPs electrocatalytic activity toward WOR. The chronoamperometric current recorded at a fixed potential of +1.35 V was selected as the analytical signal, allowing the quantification of Au@Pt/Au NPs at 1013 NPs/mL levels. The optimized electrocatalytic method was applied to the quantification of conformationally altered p53 peptide Alzheimer's disease (AD) biomarker in a competitive immunoassay using magnetic bead (MB) platforms at levels as low as 66 nM. The performance of the system in a real scenario was demonstrated analyzing plasma samples from a cognitively healthy subject. This novel Au@Pt/Au NPs-based electrocatalytic immunoassay has the advantage, over common methods for NP tags electrochemical detection, of the signal generation in the same neutral medium where the immunoassay takes place (0.1 M PBS pH 7.2), avoiding the use of additional and more hazardous reagents and paving the way to future integrated biosensing systems.

Neuroinflammatory Processes, A1 Astrocyte Activation and Protein Aggregation in the Retina of Alzheimer's Disease Patients, Possible Biomarkers for Early Diagnosis.

Alzheimer’s disease (AD), a primary cause of dementia in the aging population, is characterized by extracellular amyloid-beta peptides aggregation, intracellular deposits of hyperphosphorylated tau, neurodegeneration and glial activation in the brain. It is commonly thought that the lack of early diagnostic criteria is among the main causes of pharmacological therapy and clinical trials failure; therefore, the actual challenge is to define new biomarkers and non-invasive technologies to measure neuropathological changes in vivo at pre-symptomatic stages. Recent evidences obtained from human samples and mouse models indicate the possibility to detect protein aggregates and other pathological features in the retina, paving the road for non-invasive rapid detection of AD biomarkers. Here, we report the presence of amyloid beta plaques, tau tangles, neurodegeneration and detrimental astrocyte and microglia activation according to a disease associated microglia phenotype (DAM). Thus, we propose the human retina as a useful site for the detection of cellular and molecular changes associated with Alzheimer’s disease.

Spatial correlations exploitation based on nonlocal voxel-wise GWAS for biomarker detection of AD.

Potential biomarker detection is a crucial area of study for the prediction, diagnosis, and monitoring of Alzheimer's disease (AD). The voxelwise genome-wide association study (vGWAS) is widely used in imaging genomics studies that is usually applied to the detection of AD biomarkers in both imaging and genetic data. However, performing vGWAS remains a challenge because of the computational complexity of the technique and our ignorance of the spatial correlations within the imaging data. In this paper, we propose a novel method based on the exploitation of spatial correlations that may help to detect potential AD biomarkers using a fast vGWAS. To incorporate spatial correlations, we applied a nonlocal method that supposed that a given voxel could be represented by weighting the sum of the other voxels. Three commonly used weighting methods were adopted to calculate the weights among different voxels in this study. Then, a fast vGWAS approach was used to assess the association between the image and the genetic data. The proposed method was estimated using both simulated and real data. In the simulation studies, we designed a set of experiments to evaluate the effectiveness of the nonlocal method for incorporating spatial correlations in vGWAS. The experiments showed that incorporating spatial correlations by the nonlocal method could improve the detecting accuracy of AD biomarkers. For real data, we successfully identified three genes, namely, ANK3, MEIS2, and TLR4, which have significant associations with mental retardation, learning disabilities and age according to previous research. These genes have profound impacts on AD or other neurodegenerative diseases. Our results indicated that our method might be an effective and valuable tool for detecting potential biomarkers of AD.

Alzheimer Disease Biomarker Detection Through Electrocatalytic Water Oxidation Induced by Iridium Oxide Nanoparticles

AbstractIridium oxide nanoparticles (IrO2 NPs) synthesized following a previously reported chemical route are presented as novel tags for immunosensing taking advantage of their electrocatalytic activity towards water oxidation reaction (WOR). Cyclic voltammetry and chronoamperometry for the evaluation of the IrO2 NPs electrocatalytic activity towards WOR at neutral pH were used. The chronoamperometric current recorded at a fixed potential of +1.3 V constituted the analytical signal allowing the quantification of IrO2 NPs at nM levels. Modification of the surface of citrate‐capped IrO2 NPs with anti‐Apolipoprotein E antibodies (αApoE) was successfully achieved and the as‐prepared conjugates were used for the electrocatalytic detection of ApoE Alzheimer disease (AD) biomarker in a magnetosandwich immunoassay, reaching a detection limit of 68 ng/mL. Human plasma of a patient suffering AD was also evaluated, estimating an ApoE concentration of 20 µg/mL which is in concordance with the obtained in previously reported approaches. This novel IrO2 NPs based electrocatalytic assay presents the advantage of the signal generation in the same medium where the immunoassay takes place (PBS, pH 7.4) avoiding the use of additional reagents which also opens the way to future integrated biosensing systems and platforms with interest for other proteins as well as DNA and cells analysis.