Biomarkers and diagnostic methods for Alzheimer's disease and other neurodegenerative disorders
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Assignees
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Publication Number
US-11619637-B2
Publication Date
2023-04-04
Expiration Date
Abstract
The present invention relates to biomarkers and diagnostic and prognostic methods for Alzheimer's disease and other neurodegenerative disorders. The invention also provides compositions for detecting the biomarker as well as compositions and methods useful for treating Alzheimer's disease and other neurodegenerative disorders.
Core Innovation
The invention relates to biomarkers and diagnostic/prognostic methods for neurodegenerative disorders, including Alzheimer’s disease, using vesicles and exosomes isolated from biological samples. Biological samples comprise whole blood, serum, plasma, and cerebrospinal fluid (CSF), with biomarker panels measured in vesicles/exosomes. The described biomarkers include Tau and phosphorylated Tau, Aβ1-42, TDP-43, α-synuclein, IRS-1 and phosphorylated IRS-1 (P-S312 and P-panY), CTSD, LAMP1, ubiquitinylated proteins, HSP70, NSE, NFL, and exosome markers CD9, CD63, CD81, and CD171.
The methods describe isolating exosomes by contacting the biological sample with an antibody under conditions wherein exosomes bind the antibody to form an exosome–antibody complex for isolation. The selected exosomes are from the group consisting of neuron-derived exosomes, astrocyte-derived exosomes, oligodendrocyte-derived exosomes, and microglia-derived exosomes. Example antibody targets include anti-NCAM antibody, anti-CD171 antibody, anti-CD9 antibody, and anti-CD81 antibody for selecting particular exosome populations.
After isolation, the invention detects one or more proteins or phosphorylated proteins from the isolated exosomes using an immunoassay. The disclosed approach measures biomarker levels in exosomes and/or in antibody–vesicle complexes for diagnosing and prognosing, including identifying at-risk subjects. The document also describes related compositions and kits, including antibodies to vesicles and biomarkers and optional primers/probes for mRNA/miRNA, and a computer algorithm for analysis.
Claims Coverage
The partial content identifies one independent claim covering antibody-based isolation of selected exosome populations from whole blood, serum, or plasma followed by immunoassay detection of proteins or phosphorylated proteins. The independent claim specifies multiple inventive feature options for exosome selection and multiple antibody targets.
Antibody isolation forming exosome–antibody complex
Isolating exosomes by contacting the biological sample with an antibody under conditions wherein the exosomes present in the biological sample bind to the antibody to form an exosome–antibody complex, thereby isolating the exosomes from the sample.
Immunoassay detection of proteins or phosphorylated proteins from isolated exosomes
Detecting one or more proteins or phosphorylated proteins from the isolated exosomes with an immunoassay.
Use of whole blood, serum, or plasma biological sample
Performing the method wherein the biological sample is whole blood, serum, or plasma.
Selection of exosomes from defined cell-derived groups
Selecting the exosomes from the group consisting of neuron-derived exosomes, astrocyte-derived exosomes, oligodendrocyte-derived exosomes, and microglia-derived exosomes.
Antibody targets for selecting specific exosome populations
Using an antibody that is an anti-NCAM antibody and/or an anti-CD171 antibody, and/or an anti-CD9 antibody, and/or an anti-CD81 antibody.
Overall, the claim coverage centers on isolating selected lineage-derived exosomes from whole blood, serum, or plasma via antibody binding to form an exosome–antibody complex, then detecting one or more proteins or phosphorylated proteins from the isolated exosomes using an immunoassay, using specified antibody targets.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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