215 results about "Amyloid" patented technology

Herein are provided bispecific anti-human A-beta / human transferrin receptor antibodies and methods of using the same.

The invention belongs to the technical field of analytical chemistry and the field of early screening of Alzheimer's disease, and particularly relates to an array sensor based on zirconium-based MOF nano-enzyme and application of the array sensor to detection of amyloid protein. The zirconium-based MOF nano-enzyme for detecting amyloid protein comprises UiO-66 (at) Pt, UiO-66 (at) Pd and UiO-66 (at) PtPd, and the array sensor based on the zirconium-based MOF nano-enzyme is constructed by sensing units which are respectively added with the UiO-66 (at) Pt, the UiO-66 (at) Pd and the UiO-66 (at) PtPd. According to the amyloid protein detection method based on the zirconium-based MOF nano-enzyme, rapid and sensitive detection of amyloid protein can be realized, the cost is low, the repeatability is good, and a new idea is provided for detection of amyloid protein related diseases.

A method of pre-screening a human subject for a clinical trial for treatment of tauopathy or an amyloidogenic disease. The method comprises obtaining a plasma sample from the subject and determining a concentration of p217+tau present in the plasma sample. The method further comprises indicating the subject for further screening for the clinical trial when the concentration of p217+tau present in the plasma sample is greater than or equal to a minimum threshold and less than or equal to a maximum threshold. The minimum threshold corresponds to an amount of p217+tau in plasma over which subjects present with mild cognitive impairment (MCI) and an increased accumulation of tau tangles in the brain as compared to a cognitively normal patient. The maximum threshold corresponds to an amount of p217+tau present in plasma over which subjects present with pathology of widespread accumulation of tau tangles in multiple regions of the brain.

The invention discloses an application of ARN2966 in the treatment of UMOD (Urban Molecular Orthodontic Disease) gene mutant autosomal dominant hereditary renal tubular interstitial nephropathy (ADTKD), and belongs to the field of biomedicine. The ARN2966 has the advantages that the ARN2966 can be used for the treatment of UMOD gene mutant autosomal dominant hereditary ADTKD, and the ARN2966 can be used for the treatment of UMOD gene mutant autosomal dominant hereditary ADTKD; the application comprises the application of the amyloid precursor protein (APP)-CD74 signal axis blocking agent in the preparation of the medicine for treating the hereditary tubulointerstitial nephropathy, and the application comprises the application of the amyloid precursor protein (APP)-CD74 signal axis blocking agent in the preparation of the medicine for treating the hereditary tubulointerstitial nephropathy. Compared with the prior art, the key effect of an APP-CD74 signal axis in ADTKD-Umod pathogenesis is disclosed for the first time, and ARN2966 provides a brand new intervention strategy for treatment of ADTKD-Umod through targeted regulation and control of the pathway. Compared with a broad-spectrum anti-inflammatory drug, the ARN2966 has high targeting specificity, and side effects caused by non-specific immunosuppression can be avoided. Although the ARN2966 does not enter a clinical research stage at present, due to the unique action mechanism and verified safety characteristics of the ARN2966, the ARN2966 has remarkable transformation medical value and clinical application prospect in the aspect of developing ADTKD-Umod targeted therapeutic drugs.

The invention relates to the technical field of electrochemical analysis and detection, in particular to an electrochemical biosensor based on CRISPR / Cas12a as well as a preparation method, a detection method and application of the electrochemical biosensor. An electrochemical biosensor based on CRISPR / Cas12a comprises a Cas12a-crRNA detection system, an APT-ActDNA adaptation system and an electrochemical aptamer sensor, and when a target analyte exists, the Cas12a-crRNA detection system and the APT-ActDNA adaptation system are matched with each other to react with the target analyte, so that the electrochemical aptamer sensor generates an electrochemical signal. According to the technical scheme, the problems of specific recognition and detection of amyloid beta peptide (Abeta) in a complex biological sample are solved, the preparation method is simple, the cost is low, and the detection method is high in sensitivity and accuracy.

The invention provides a pharmaceutical composition for treating Alzheimer's disease. The pharmaceutical composition is prepared from the following raw materials in parts by weight: 10-15 parts of ginseng, 10-15 parts of rhizoma acori graminei, 10-15 parts of polygala tenuifolia, 15-20 parts of rhizoma polygonati, 15-20 parts of ginkgo leaves and 5-10 parts of schisandra chinensis. Therefore, the ginseng and the ginkgo leaves jointly regulate a cholinergic system and cerebral blood flow, and the cognitive function is enhanced; the rhizoma acori graminei and the ginkgo leaves cooperate to inhibit aggregation of beta-amyloid protein, improve cerebral circulation and relieve neurotoxicity. Polygonatum sibiricum and Chinese magnoliavine fruit protect nerve cells through anti-oxidation and anti-inflammatory effects and reduce nerve injury. Schizandrin further stabilizes a neurotransmitter system and enhances the synergistic effect of other medicinal materials, a multi-layer treatment network of Abeta deposition inhibition, cholinergic system regulation, anti-inflammation and anti-oxidation and nerve protection is integrally formed, and the core pathological link of the Alzheimer's disease is comprehensively intervened, so that the cognitive function is improved, and the disease progress is delayed.

The present invention relates to a composition for preventing, alleviating or treating cognitive disorders or Alzheimer's disease, comprising a Lactobacillus delbrueckii subsp. Lactis strain as an active ingredient. The present invention provides a composition for preventing, alleviating or treating cognitive disorders or Alzheimer's disease (AD), comprising a Lactobacillus delbrueckii subsp. Lactis strain as an active ingredient. The strain of the present invention has excellent effects of reducing amyloid beta protein (A beta) or tau protein (Tau) and improving cognitive function, and thus can be usefully used as a composition for preventing, alleviating or treating cognitive impairment or AD.

The application discloses a kind of cognitive promotion method and system based on multi-modal data.The cognitive promotion method includes: obtaining the first multi-modal data before treatment of patient;Amyloid load grouping is carried out to patient based on the amyloid load in the brain of patient, to obtain the initial cognitive training scheme corresponding;Cognitive training is carried out based on initial cognitive training scheme during the treatment of patient, and the second multi-modal data during treatment is collected;Based on multi-modal data before and after treatment of patient, in combination with brain network group atlas, obtain the multi-modal change data of patient;The multi-modal change data of patient is input into preset model, to output the cognitive promotion scheme that cognitive index of patient is most improved, to push to patient and carry out cognitive training.The method will be integrated by A beta-PET data, functional nuclear magnetic resonance imaging data and event-related potential data, real-time evaluation of the neuroplasticity change of patient, to dynamically generate personalized cognitive promotion scheme.

This invention discloses a method and system for following up on magnetic resonance imaging (MRI) images of amyloid-related radiological abnormalities, belonging to the field of medical image processing. The method includes: acquiring multimodal MRI image data; performing bias field correction and intensity normalization based on a bias field fitting model to generate a first image set; performing global alignment and edge detection on the first image set to extract anatomical physical boundaries, generating brain region mask data; performing branch deformation field registration on the first image set within the brain parenchyma defined by the brain region mask data to generate a spatially aligned second image set; calculating the average intensity of normal brain parenchyma regions in the second image set to obtain a scaling factor, acquiring a three-dimensional residual image; performing anisotropic diffusion filtering denoising on the three-dimensional residual image, and performing differential denoising and morphological screening processing, outputting the detection results. This invention eliminates systematic artifacts caused by insufficient bias field correction.

To provide antibodies and antigen binding fragments thereof that are useful for diagnosis, prognosis and treatment of Alzheimer's disease or other β-amyloid-related diseases, and methods of making and using the antibodies or antigen binding fragments thereof.SOLUTION: The present invention provides an isolated monoclonal antibody or antigen-binding fragment thereof, comprising a heavy chain complementarity determining region 1 (HCDR1), HCDR2, HCDR3, a light chain complementarity determining region 1 (LCDR1), LCDR2, and LCDR3, having specific polypeptide sequences, wherein the antibody or antigen-binding fragment thereof specifically binds 3pE Ab, preferably human 3pE Ab.SELECTED DRAWING: None

The invention discloses an application of a pyruvate dehydrogenase kinase (PDKS) inhibitor in preparation of a composition for treating Alzheimer's disease (AD), and particularly discloses an application of the PDKs inhibitor in preparation of the composition for treating the AD. According to the invention, the level of oxidative phosphorylation (OXPHOS) of microglial cells is obviously enhanced, the inflammatory response of the microglial cells is effectively reduced, the migration and aggregation capabilities of the microglial cells are obviously improved, the capability of the microglial cells to phagocytize and degrade extracellular beta-amyloid protein (A beta) plaque is obviously enhanced, the cognitive function defect of AD model mice is effectively improved, and the application of the microglial cells in the treatment of the AD model mice is promoted. The preparation is simple, and the application is wide.

The present application is applicable to the field of material technology, and provides a hollow nanocomposite material and its preparation method and application. The structural formula of the hollow nanocomposite material is Au NBPs@CuS, wherein CuS is an outer semiconductor and Au NBPs is an inner core. The present application is a nanostructure with a gold nanobipyramid as the inner core and a hollow p-type semiconductor as the outer layer, which realizes the first combination of p-type semiconductor and gold nanobipyramid. The tip effect of Au NBPs is better than that of previous Au NPs, and its ultraviolet absorption reaches a maximum at 808nm, and its phototherapy performance is greatly improved. By compounding Au NBPs with CuS, not only its photothermal performance is greatly improved, the photothermal conversion efficiency reaches 43.88%, and it can generate active oxygen under light. 1 O2 and ·OH, their excellent photothermal effect and photodynamic properties provide theoretical support for their application in inhibiting amyloid protein aggregation.

The invention discloses a non-degreasing biological tissue dyeing method and device. The dyeing method of the non-degreasing biological tissue comprises the following steps: a sample fixing step: fixing a biological tissue sample by adopting paraformaldehyde and / or glutaraldehyde; and a dyeing step: carrying out electrophoresis dyeing on the fixed biological tissue sample which is not degreased by using a nucleic acid dye and a beta-amyloid protein small molecule dye. According to the non-degreasing biological tissue dyeing method disclosed by the invention, the non-degreasing biological tissue is directly dyed, so that the damage of degreasing operation to a sample is avoided; moreover, the nucleic acid dye is combined with the beta-amyloid protein small molecule dye, so that the whole brain sample can be quickly and efficiently dyed, and high-resolution fluorescence labeling and three-dimensional space distribution imaging of beta-amyloid protein plaques in the whole brain range can be realized; the method is of great significance in revealing the spatial distribution pattern of beta-amyloid protein and explaining the pathogenesis of Alzheimer's disease.

Antibodies that bind human beta-amyloid peptide, methods of detecting, measuring and treating amyloidogenic disorders with said antibodies, pharmaceutical compositions comprising the antibodies and methods of manufacture are provided.

The present invention relates to polymorphs of a nitrogen-containing heterocyclic compound. The polymorphs of the present invention can effectively enhance or reactivate synaptic plasticity, and inhibit or eliminate the accumulation of beta-amyloid, without causing side effects, thereby exerting a therapeutic effect on various nervous system diseases or neurodegenerative diseases. In addition, the polymorphs of the present invention exhibit excellent physicochemical properties, such as stability, solubility, hygroscopicity, and mechanical strength, and show excellent permeability to the blood-brain barrier (BBB).

The present invention provides the use of Yangxue Oral Liquid in the preparation of drugs for neuroprotection against Alzheimer's disease and / or Parkinson's disease, and belongs to the field of biopharmaceutical technology. The present invention provides the use of Yangxue Oral Liquid in the preparation of drugs for neuroprotection against Alzheimer's disease and / or Parkinson's disease. By verifying the effects of Yangxue Oral Liquid on the amyloid beta-induced neuronal apoptosis model, the cobalt chloride-induced SH‑SY5Y cell hypoxia model, and the LPS-induced SH‑SY5Y cell inflammation model, the results showed that Yangxue Oral Liquid has a neuroprotective effect against Alzheimer's disease and / or Parkinson's disease. Therefore, the application provided by the present invention provides a new means for neuroprotection against Alzheimer's disease and / or Parkinson's disease.

The present invention relates to a water-soluble compound for the detection of beta-amyloid, and a production method thereof. The compound according to the present invention has excellent water-soluble properties, and thus can provide a water-soluble formulation for the detection of beta-amyloid. Accordingly, there is an effect that the compound can be useful as a composition for the detection of beta-amyloid through retinal imaging.

The invention discloses ICA1L derived peptide and application thereof in relieving Alzheimer disease A beta pathology. The amino acid sequence of the ICA1L derived peptide is shown as SEQ ID NO.01. The invention further discloses a preparation method of the ICA1L derived peptide. The compound can be combined with low-density lipoprotein receptor associated protein 1 (LRP1), inhibit K48 connection type ubiquitination of the LRP1 and prevent degradation through a proteasome pathway, so that the protein level of the LRP1 is stabilized, and the expression of beta-site APP lyase 1 is reduced to reduce the generation and deposition of beta-amyloid protein. In vitro, the peptide shows good biocompatibility and cell uptake ability; in vivo, the peptide has blood-brain barrier permeability, can be positioned in neurons, can significantly reduce hippocampus and cortex A beta plaque deposition in a 5xFAD mouse model through caudal vein injection, reduces BACE1 and beta-CTF levels, and improves the cognitive function. The invention further discloses an ICA1L-LRP1 regulatory axis, and a new strategy is provided for treatment of the Alzheimer's disease.

The application discloses a photosensitizer targeting beta amyloid, and a preparation method and application thereof. The photosensitizer is a photosensitizer with A-D-A configuration, and a structural formula thereof is shown as formula I. The photosensitizer synthesized in the application has a longer emission wavelength, and after being combined with beta amyloid, the fluorescence signal is obviously enhanced, and can effectively generate singlet oxygen, that is, the photosensitizer can target mark A beta protein, and is used for fluorescence imaging of the A beta protein; and after the photosensitizer synthesized in the application is combined with beta amyloid in the brain of an Alzheimer's disease (AD) model mouse, the cognitive ability of the AD mouse can be effectively improved, A beta-mediated neurotoxicity can be reduced, and clearance of A beta plaques can be promoted, that is, the photosensitizer can be used for early diagnosis and treatment of Alzheimer's disease.

A fusion molecule having phagocytosis-inducing activity is disclosed. The fusion molecule contains a first region capable of binding a TAM receptor and a second region capable of binding to a target substance of which aberrant accumulation is associated with or characteristic of diseases. The fusion molecule effectively clears and / or reduces and / or suppresses accumulated abnormal proteins, such as beta-amyloid, tau, alpha-synuclein, huntingtin, or prion, or the like. Uses of the fusion molecule are disclosed. The fusion molecule can be used for prevention or treatment of proteinosis caused by the abnormal accumulation of substances.

The composition for predicting Alzheimer's disease prognosis comprising a detection reagent that specifically binds to any one or more genes selected from the group consisting of Nos1 (Nitric oxide synthase 1), Aph1B (Anterior pharynx defective 1 homolog B), Ryr3 (Ryanodine receptor 3), Atf6 (Activating transcriptional factor 6), Ip3r (Inositol trisphosphate receptor), Nep (Neprilysin), Cdk5 (cyclin dependent kinase 5) and Abad (Amyloid beta-binding alcohol dehydrogenase), a kit, and a method for providing information on Alzheimer's disease prognosis of the present invention can rapidly and accurately predict the prognosis of Alzheimer's disease, and can determine the prognosis for a drug by comparing the expression level before and after drug administration, so that an appropriate treatment direction can be determined according to the predicted prognosis. Therefore, they have an effect that can greatly contribute to the reduction of mortality due to Alzheimer's disease.

The present invention relates to an improved antibody specifically binding to amyloid-β oligomers (AβOs). Specifically, the present invention relates to an improved form of the antibody W20. Compared with the antibody W20, the improved form of the antibody W20 has a significantly improved affinity to AβOs, and can more significantly inhibit the aggregation of Aβ and the AβOs-induced toxicity of nerve cells, more effectively improve the cognition and memory functions of an Alzheimer's disease model mouse, and reduce pathological changes in the brain of the mouse. The improved form of the antibody can specifically bind to oligomers of an amyloid-β, α-synuclein, mHTT and SOD 1, can inhibit the aggregation and cytotoxicity of various amyloids, and has a better potential for treating various amyloid diseases, such as Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, than the antibody W20. The improved form of the antibody can specifically bind to a highly toxic amyloid protein oligomer Aβo*3F, and has a better AD diagnosis value. The amino acid sequence of the antibody W20 is as shown in SEQ ID NO: 1.

A pyrimidine-2,4-diamine compound and a preparation method and application thereof are provided. The pyrimidine-2,4-diamine compound of the present disclosure can be used in the research of biological or pharmacological phenomena and cathepsin C-involved signal pathway transduction and the evaluation of novel cathepsin C inhibitors. The pyrimidine-2,4-diamine compound is subjected to the screening of anti-cathepsin C activity in vitro and in vivo and proved to have strong inhibitory activity on cathepsin C. The pyrimidine-2,4-diamine compound is subjected to the screening of anti-NSP activity in vivo and proved to have strong inhibitory activity on NSP. The pyrimidine-2,4-diamine compound is subjected to the screening of anti-inflammatory activity in vivo and proved to have an effective therapeutic effect on inflammatory disease models. Meanwhile, the pyrimidine-2,4-diamine compound shows low toxicity and exhibits good application prospect.

The invention discloses a myocardial amyloidosis quantitative analysis method based on SPECT imaging and related equipment, and relates to the field of wisdom medical device.The method comprises the steps that firstly, three-dimensional SPECT original data of N time phases of a target patient in the cardiac cycle are collected, a mu graph is generated based on low-dose CT for registration and attenuation correction, and a dynamic image is reconstructed; and then an MR structure sequence under synchronous electrocardio gating is obtained, and SPECT and MR space standardization and partial volume effect correction processing are completed. And unifying the cardiac cycle image form through affine and nonlinear transformation, and generating a high-quality enhanced SPECT image. Finally, radioactive counting information is extracted on the basis of three-dimensional segmentation, multiple myocardial quantitative indexes are calculated, comprehensive analysis of myocardial functions is achieved in combination with left ventricular functional parameters, and accurate image support is provided for non-invasive diagnosis and curative effect evaluation of myocardial amyloidosis.

The present invention relates to a composite material comprising at least one textile universal polymer and protein fibres containing at least one amyloid structure. The invention also relates to a method for preparing such a material and to the use of such a material for adsorbing contaminants or extracting metal ions.

The application belongs to the technical field of medical imaging, and particularly relates to brain-targeting APP@Dextran-Fe3O4 nanoparticles as well as a preparation method and application thereof. The APP@Dextran-Fe3O4 nanoparticles provided by the application can act on the beta amyloid protein receptor in the brain through a non-invasive intravenous injection mode, thereby realizing the transport across the blood-brain barrier, and having a higher accumulation in the brain of Alzheimer's disease patients, especially in the hippocampus which is the main lesion site of Alzheimer's disease. In combination with the high resolution and high sensitivity characteristics of MPI imaging, the diagnosis of Alzheimer's disease can be realized. Meanwhile, pathological analysis shows that the APP@Dextran-Fe3O4 nanoparticles have the effects of inhibiting the inflammatory reaction in the brain of Alzheimer's disease and reducing the apoptosis of neuron cells, and have certain benefits for slowing down Alzheimer's disease.

The present disclosure relates to disaccharides with defined sulfation patterns, and oligosaccharide mimetics comprising the disaccharides as repeating units linked in a head to tail fashion. The present disclosure further relates to methods of making the same, and to methods of using the same to mediate cell proliferation, cell differentiation, amyloid plaque formation, anti-coagulation, and neuronal growth.

This invention discloses a sulfated arabinoglycoside, its preparation method, and its applications, belonging to the field of biomedical technology. The technical solution includes a sulfated arabinoglycoside derived from *Streptococcus linearis* polysaccharide; a degree of polymerization of 2-5; arabinose as the main monosaccharide, and containing galactose; the molar percentage of arabinose is not less than 80%, and the molar percentage of galactose is not more than 20%; the main chain is composed of (1→4)-β-L-pyranose arabinose groups, with the sulfate groups of the arabinose mainly substituted at the C-3 position. This invention is applied to inhibiting the abnormal aggregation of human pancreatic islet amyloid peptide (hIAPP), solving the problem of the lack of safe and effective intervention methods for the abnormal aggregation of human pancreatic islet amyloid peptide in existing technologies. It features stable raw material sources, high safety, a simple and mild preparation method suitable for large-scale preparation, and the ability to inhibit the abnormal aggregation of human pancreatic islet amyloid peptide and reduce pancreatic β-cell damage.

The present invention relates to a substance that can serve as a surrogate for amyloid spheroids (ASPD) and an analysis method for ASPD. In one embodiment, the present disclosure relates to a substance formed by cross-linking amyloid β (Aβ) using a cross-linking agent having a spacer arm length of at least 100 and no longer than 1000, or a cross-linking agent having 1 or more and no more than 13 oxyethylene (-CH2CH2O-) and / or oxypropylene (-CH2CH2CH2O-) groups as spacer arms. In another embodiment, the present disclosure relates to an analysis method for ASPD using the substance as a standard substance.

The application belongs to the technical field of biological medicine and molecular biology, and particularly relates to application of umbilical cord blood plasma-derived extracellular vesicles and related bioactive molecules thereof in treatment of Alzheimer's disease. Specifically, the application isolates extracellular vesicles (UCBP-sEVs) from umbilical cord blood plasma, which has the effect of improving Alzheimer's disease. Further research finds that high enrichment of miR-16-2-3p therein is a key molecule for mediating treatment of Alzheimer's disease. miR-16-2-3p targets and inhibits expression of ROCK2, reduces phosphorylation level of TFEB and promotes nuclear translocation of the same, activates microglial autophagy-lysosome pathway, and thus promotes phagocytosis and degradation of intracerebral beta amyloid, and therefore has good practical application value.