The present disclosure relates generally to the field of neurology. In particular, the disclosure relates to a method of detecting a neurodegenerative disease in a subject and methods of treatment thereof. The methods include detecting the level of an exosome-bound aggregated biomarker in a sample obtained from the subject, wherein an increased level of the exosome-bound aggregated biomarker as compared to a reference indicates that the subject is suffering from a neurodegenerative disease. Also described are methods for detecting a subject at risk of developing amyloidosis or a neurodegenerative disease, methods for detecting and treating amyloidosis or a neurodegenerative disease in a subject, and methods of determining the aggregation state of a biomarker in a sample.

The present invention includes methods and kits for the diagnosing a neurological disease within primary care settings comprising: obtaining a blood test sample from a subject, measuring IL-7 and TNFα biomarkers in the blood sample, comparing the level of the one or a combination of biomarkers and neurocognitive screening tests with the level of a corresponding one or combination of biomarkers in a normal blood sample and neurocognitive screening tests, and predicting that an increase in the level of the blood test sample in relation to that of the normal blood sample indicates that the subject is likely to have a neurological disease.

The present invention is a method for detecting a specific disease based on the result of a measurement in which the amount of a peptide serving as a biomarker contained in a biological sample is determined by using an LC-MS. A pretreatment process performed before the measurement using the LC-MS includes the steps of preparing a mixed sample solution by adding a stable isotope reagent and a trifluoroacetic acid to the biological sample, where the stable isotope reagent is prepared beforehand by labeling the peptide with a stable isotope; boiling the mixed sample solution; injecting the mixed sample solution after boiled into a solid-phase extraction column to make the peptide be retained in the solid-phase extraction column; and passing a water-soluble organic solvent through the solid-phase extraction column to elute the peptide retained in the solid-phase extraction column and collect the eluate.

Two different antibodies that specifically bind to tau protein or phosphorylated tau protein are used. One of the two different antibodies is a first antibody immobilized on a support or labeled with a molecule capable of binding to the support, and the other of the two different antibodies is a second antibody labeled without being immobilized on the support. The tau protein includes an N-terminal domain, a C-terminal domain, and an intermediate domain located between the N-terminal and C-terminal domains. Epitopes recognized by the first and second antibodies are each an amino acid sequence contained in the intermediate domain or an amino acid sequence contained in the N-terminal domain. One of the first and second antibodies is first subjected to an antigen-antibody reaction with the blood sample, and the other of the first and second antibodies is subsequently subjected to an antigen-antibody reaction with the blood sample.

The invention provides anti-Tau antibodies and methods of using the same.

Provided herein are compositions and methods for reducing toxicity associated with TAR DNA-binding protein 43. Certain embodiments of the present disclosure are related to compositions that treat, inhibit, reduce, prevent, or delay a disease or condition associated with TDP-43 toxicity, such as cystic fibrosis or neurodegenerative diseases. Certain embodiments of the present disclosure are related to methods of treating, inhibiting, reducing, preventing, or delaying a disease or condition associated with TDP-43 toxicity by administering compounds of any one of Formulas (I), (II), (III), (IV), (V), (VI), (VII), or (VIII) to a subject in need.

Methods and compositions for detecting tau pathology are described. The compositions for detecting tau pathology comprise a targeting ligand that specifically binds to a cell surface marker of tau pathology, wherein the targeting ligand is linked to a liposome that includes an imaging agent. The compositions can be used in a method for imaging tau pathology in a subject that comprises administering to the subject an effective amount of the composition to a subject and imaging at least a portion of the subject to determine if that portion of the subject exhibits tau pathology. The compositions can also be used to detect tau pathology in biological samples obtained from a subject.

The invention relates to inhibitors of CDK12 (cyclin-dependent kinase 12), and there use in the treatment or prevention of a disorder in a subject caused by the generation of repeat expansion transcripts.

The present application relates to a non-human mammal model of a human neurodegenerative disorder, methods of producing the non-human mammal model, and methods of using the non-human mammal model to identify agents suitable for treating a neurodegenerative disorder. The present application also relates to methods of treating neurodegenerative disorders and restoring normal brain interstitial potassium levels.

The present invention is in the field of transactive response DNA binding protein with a molecular weight of 43 kDa (TARDB or also TDP-43). The invention relates to TDP-43 specific binding molecules, in particular to anti-TDP-43 antibodies or an antigen-binding fragment or a derivative thereof and uses thereof. The present invention provides means and methods to diagnose, prevent, alleviate and/or treat a disease, disorder and/or abnormality associated with TDP-43 aggregates including but not limited to Frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Chronic Traumatic Encelopathy (CTE), and limbic-predominant age-related TDP-43 encephalopathy (LATE).