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A high-affinity fluorescence probe for copper(II) ions and its application in fluorescence lifetime correlation spectroscopy
摘要： Copper is one of the most important transition metals in many organisms where it catalyzes a manifold of different processes. As a result of copper’s redox activity, organisms have to avoid unbound ions, and a dysfunctional copper homeostasis may lead to multifarious pathological processes in cells with very severe ramifications for the affected organisms. In many neurodegenerative diseases, however, the exact role of copper ions is still not completely clarified. In this work, a high-affinity and highly selective copper probe molecule, based on the naturally occurring tetrapeptide DAHK is synthesized. The sensor (log KD = ? 12.8 ± 0.1) is tagged with a fluorescent BODIPY dye whose fluorescence lifetime distinctly decreases from 5.8 ns ± 0.2 ns to 0.4 ns ± 0.1 ns on binding to copper(II) cations. It is shown by using fluorescence lifetime correlation spectroscopy that the concentration of both probe and probe-copper complex can be simultaneously measured even at nanomolar concentration levels. This work presents a possible starting point for a new type of probe and method for future in vivo studies to further reveal the exact role of copper ions in organisms.
关键词： BODIPY,Single molecule detection,FLIM,Alzheimer,ATCUN motif,Parkinson,DAHK
更新于2025-11-21 11:24:58
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Graphene oxide-quenching-based fluorescence in situ hybridization (G-FISH) to detect RNA in tissue: Simple and fast tissue RNA diagnostics
摘要： FISH-based RNA detection in paraffin-embedded tissue can be challenging, with complicated procedures producing uncertain results and poor image quality. Here, we developed a robust RNA detection method based on graphene oxide (GO) quenching and recovery of fluorescence in situ hybridization (G-FISH) in formalin-fixed paraffin-embedded (FFPE) tissues. Using a fluorophore-labeled peptide nucleic acid (PNA) attached to GO, the endogenous long noncoding RNA BC1, the constitutive protein β-actin mRNA, and miR-124a and miR-21 could be detected in the cytoplasm of a normal mouse brain, primary cultured hippocampal neurons, an Alzheimer’s disease model mouse brain, and glioblastoma multiforme tumor tissues, respectively. Coding and non-coding RNAs, either long or short, could be detected in deparaffinized FFPE or frozen tissues, as well as in clear lipid-exchanged anatomically rigid imaging/immunostaining-compatible tissue hydrogel (CLARITY)-transparent brain tissues. The fluorescence recovered by G-FISH correlated highly with the amount of miR-21, as measured by quantitative real time RT-PCR. We propose G-FISH as a simple, fast, inexpensive, and sensitive method for RNA detection, with a very low background, which could be applied to a variety of research or diagnostic purposes.
关键词： glioblastoma multiforme tumor,tissue RNA diagnostics,Graphene oxide-quenching-based fluorescence in situ hybridization (G-FISH),Alzheimer’s disease,formalin-fixed paraffin-embedded (FFPE) tissue
更新于2025-09-23 15:23:52
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Estimating $c$-level partial correlation graphs with application to brain imaging
摘要： Alzheimer’s disease (AD) is a chronic neurodegenerative disease that changes the functional connectivity of the brain. The alteration of the strong connections between different brain regions is of particular interest to researchers. In this article, we use partial correlations to model the brain connectivity network and propose a data-driven procedure to recover a c-level partial correlation graph based on PET data, which is the graph of the absolute partial correlations larger than a pre-speci?ed constant c. The proposed procedure is adaptive to the “large p, small n” scenario commonly seen in whole brain studies, and it incorporates the variation of the estimated partial correlations, which results in higher power compared to the existing methods. A case study on the FDG-PET images from AD and normal control (NC) subjects discovers new brain regions, Sup Frontal and Mid Frontal in the frontal lobe, which have different brain functional connectivity between AD and NC.
关键词： Partial correlation,High dimensionality,Alzheimer’s Disease,Brain connectivity
更新于2025-09-23 15:23:52
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PET-Liganden für die Diagnostik der Alzheimer-Demenz: Amyloid und Tau
摘要： Over the last 15 years diagnostic imaging of amyloid and tau deposits with PET has gained increasing importance especially in the context of diagnosis of dementia such as Alzheimer's disease. First radiotracers that were developed aimed at the detection of amyloid plaques in the brain. In the meantime the contribution of hyperphosphorylated proteins (TAU) that lead to another type of protein deposits is getting more and more in the focus of current research on the origin of this disease. While a number of 18F-labelled ligands for amyloid imaging have recently been granted marketing authorization and therefore are commercially available and can be used by licensed nuclear medicine physicians throughout Europe and the US, this is not true for radiotracers for TAU-protein imaging. Therefore their use is restricted to clinical trials or to the application of in house manufactured substances. This article should give an overview on characteristics, development and availability of PET tracers for amyloid and tau imaging and in addition to that exemplify the challenges associated with a GMP compliant manufacturing of these short lived radiotracers.
关键词： Alzheimer,18F,Amyloid,11C,PET,Tau
更新于2025-09-23 15:22:29
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Usefulness of peripapillary nerve fiber layer thickness assessed by optical coherence tomography as a biomarker for Alzheimer’s disease
摘要： The use of optical coherence tomography (OCT) has been suggested as a potential biomarker for Alzheimer’s Disease based on previously reported thinning of the retinal nerve fiber layer (RNFL) in Alzheimer’s disease’s (AD) and Mild Cognitive Impairment (MCI). However, other studies have not shown such results. 930 individuals (414 cognitively healthy individuals, 192 probable amnestic MCI and 324 probable AD) attending a memory clinic were consecutively included and underwent spectral domain OCT (Maestro, Topcon) examinations to assess differences in peripapillary RNFL thickness, using a design of high ecological validity. Adjustment by age, education, sex and OCT image quality was performed. We found a non-significant decrease in mean RNFL thickness as follows: control group: 100,20 ± 14,60 μm, MCI group: 98,54 ± 14,43 μm and AD group: 96,61 ± 15,27 μm. The multivariate adjusted analysis revealed no significant differences in mean overall (p = 0.352), temporal (p = 0,119), nasal (p = 0,151), superior (p = 0,435) or inferior (p = 0,825) quadrants between AD, MCI and control groups. These results do not support the usefulness of peripapillary RNFL analysis as a marker of cognitive impairment or in discriminating between cognitive groups. The analysis of other OCT measurements in other retinal areas and layers as biomarkers for AD should be tested further.
关键词： retinal nerve fiber layer,optical coherence tomography,Alzheimer’s Disease,cognitive impairment,biomarker
更新于2025-09-23 15:21:21
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Noninvasive In Situ Ratiometric Imaging of Biometals Based on Self-Assembled Peptide Nanoribbon
摘要： Development of probes for accurate sensing and imaging of biometals in situ is still a growing interest owing to their crucial roles in cellular metabolism, neurotransmission, and apoptosis. Among them, Zn2+ and Cu2+ are two important cooperative biometals closely related to Alzheimer’s disease (AD). Herein, we developed a multifunctional probe based on self-assembling peptide nanoribbon for ratiometric sensing of Zn2+, Cu2+, or Zn2+ and Cu2+ simultaneously. Uniform peptide nanoribbon (AQZ@NR) was rationally designed by coassembling a Zn2+-specific ligand AQZ-modified peptide (AQZKL-7) with peptide KL-7. The nanoribbon further combined with Cu2+-sensitive near-infrared quantum dots (NIR QDs) and Alexa Fluor 633 as an inner reference molecule, which was endowed with the capability for ratiometric Zn2+ and Cu2+ imaging at the same time. The peptide-based probe exhibited good specificity to Zn2+ and Cu2+ without interference from other ions. Importantly, the nanoprobe was successfully applied for noninvasive Zn2+ and Cu2+ monitoring in both living cells and zebrafish via multicolor fluorescence imaging. This gives insights into the dynamic Zn2+ and Cu2+ distribution in an intracellular and in vivo mode, as well as understanding the neurotoxicity of high concentration of Zn2+ and Cu2+. Therefore, the self-assembled nanoprobe shows great promise in multiplexed detection of many other biometals and biomolecules, which will benefit the diagnosis and treatment of AD in clinical applications.
关键词： fluorescence imaging,biometals,ratiometric imaging,peptide nanoribbon,Cu2+,Zn2+,self-assembly,Alzheimer’s disease
更新于2025-09-23 15:21:01
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Au nano-urchins enabled localized surface plasmon resonance sensing of beta amyloid fibrillation
摘要： Early stage detection of neurodegenerative diseases such as Alzheimer’s disease (AD) is of utmost importance, as it has become one of the leading causes of death of millions of people. The gradual intellectual decline in AD patients is an outcome of fibrillation of amyloid beta 1-42 (Aβ1-42) peptides in brain. In this paper, we present localized surface plasmon resonance (LSPR) based sensing of Aβ1-42 fibrillation using Au nano-urchins. Strongly localized field confinement at the spiky nanostructures of nano-urchin surfaces enables them to detect very low concentrations of Aβ1-42. In addition, the LSPR peak of Au nano-urchins, which is very sensitive to ambient conditions, shows significant responses at different fibrillation stages of Aβ1-42. Reduction in LSPR peak intensity with increase in the fibrillation is chosen as the sensing parameter here. This paper in this context provides LSPR based highly sensitive, label-free and real-time sensing of Aβ1-42 fibrillation that is highly advantageous compared to the existing techniques which require binding additives or fluorescent biomarkers.
关键词： Au nano-urchins,localized surface plasmon resonance,biosensing,amyloid beta,Alzheimer’s disease
更新于2025-09-23 15:19:57
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Sparse Feature Learning with Label Information for Alzheimer’s Disease Classification Based on Magnetic Resonance Imaging
摘要： Biomedical signal processing data have been used for automatic diagnosis and classification of brain disease, which is an important part of research in smart city. How to select discriminant features from these data is the key that will affect subsequent automatic diagnosis and classification performance. However, in previous manifold regularized sparse regression models, the local neighborhood structure was constructed directly in the traditional Euclidean distance without fully utilizing the label information of the subjects, which leads to the selection of less discriminative features. In this paper, we propose a novel manifold regularized sparse regression model for learning discriminative features. Specifically, we first adopt l2,1-norm regularization to jointly select a relevant feature subset among the samples. Then, to select more discriminative features, a novel manifold regularization term is constructed via the relative distance adjusted by the label information, which can simultaneously maintain the compactness of intra-class samples and the separability of inter-class samples. The proposed feature learning method is further carried out for both the binary classification and the multi-class classification. Experimental results on Alzheimer’s Disease Neuroimaging Initiative database demonstrate the effectiveness of the proposed method, which can be utilized for the diagnosis of Alzheimer’s disease and mild cognitive impairment.
关键词： feature learning,Alzheimer's disease,manifold regularization,sparse regression
更新于2025-09-19 17:15:36
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[IEEE 2018 IEEE 38th International Conference on Electronics and Nanotechnology (ELNANO) - Kiev (2018.4.24-2018.4.26)] 2018 IEEE 38th International Conference on Electronics and Nanotechnology (ELNANO) - Florbetapir Image Analysis for Alzheimer's Disease Diagnosis
摘要： Over decades Alzheimer’s disease (AD) remains without decent cure, and only disease-modifying methods are available. This paper is devoted to the analysis of amyloid-PET images with florbetapir (18F-AV-45) tracer to detect the presence of AD or Mild Cognitive Impairment (MCI). The first part of the article dedicated to image processing pipeline, specifically, spacial normalisation and feature extraction. The second part is devoted to the development of the multiclass classifier with deep learning methods. In particular, deep neural network was developed to distinguish three stages: health control (HC), MCI and AD. After tuning and training a neural network, the final specificity of 78% and sensitivity of 90% has been achieved.
关键词： Deep learning,Florbetapir,PET imaging,Alzheimer's disease,Amyloid Imaging
更新于2025-09-19 17:15:36
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Femtomolar sensing of Alzheimer's tau proteins by water oxidation-coupled photoelectrochemical platform
摘要： Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder. A key pathogenic event of AD is the formation of intracellular neurofibrillary tangles that are mainly composed of tau proteins. Here, we report on ultrasensitive detection of total tau (t-tau) proteins using an artificial electron donor-free, BiVO4-based photoelectrochemical (PEC) analysis. The platform was constructed by incorporating molybdenum (Mo) dopant and iron oxyhydroxide (FeOOH) ad-layer into the BiVO4 photoelectrode and employing a signal amplifier formed by horseradish peroxidase (HRP)-triggered oxidation of 3,3′-diaminobenzidine (DAB). Despite the absence of additional electron suppliers, the FeOOH/Mo:BiVO4 conjugated with the Tau5 antibody produced strong current signals at 0 V (vs. Ag/AgCl, 3M NaCl) under the illumination of a white light-emitting diode. The Mo extrinsic dopants increased the charge carrier density of BiVO4-Tau5 by 1.57 times, and the FeOOH co-catalyst promoted the interfacial water oxidation reaction of Mo:BiVO4-Tau5 by suppressing charge recombination. The introduction of HRP-labeled Tau46 capture antibodies to the FeOOH/Mo:BiVO4-Tau5 platform produced insoluble precipitation on the transducer by accelerating the oxidation of DAB, which amplified the photocurrent signal of FeOOH/Mo:BiVO4-Tau5 by 2.07-fold. Consequently, the water oxidation-coupled, FeOOH/Mo:BiVO4-based PEC sensing platform accurately and selectively recognized t-tau proteins down to femtomolar concentrations; the limit of detection and limit of quantification were determined to be 1.59 fM and 4.11 fM, respectively.
关键词： Alzheimer’s disease,water oxidation,Femtomolar sensitivity,tau proteins,BiVO4
更新于2025-09-19 17:13:59