Tropomyosin isoforms related to alzheimers disease and mild cognitive impairment
Inventors
Zellner, Maria • Umlauf, Ellen
Assignees
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Publication Number
US-9927429-B2
Publication Date
2018-03-27
Expiration Date
Abstract
The present invention provides an in vitro method to aid the diagnosis of Alzheimer's disease (AD) or Mild Cognitive Impairment (MCI), comprising determining the level of expression of one or more tropomyosin isoform(s) corresponding to P09493-3 and/or P09493-1 in a patient's sample. A kit comprising probes that bind to tropomyosin isoforms P09493-3 and P09493-1 is also provided.
Core Innovation
The invention relates to an in vitro diagnostic approach for Alzheimer’s disease (AD) and mild cognitive impairment (MCI) by measuring expression levels of tropomyosin isoform(s) corresponding to P09493-3 and/or P09493-1 in a patient sample. The approach compares the measured expression level in a sample to results from a normal control sample from subject(s) that do not have Alzheimer’s Disease or Mild Cognitive Impairment.
The method includes contacting the sample in vitro with a first antibody or probe that binds specifically to an exon epitope of P09493-3 and P09493-1 wherein the epitope does not comprise exon 1a (SEQ ID NO:1), and a second antibody or probe that binds specifically to an exon 1a (SEQ ID NO:1) epitope of P09493-3 and P09493-1. The first and second antibodies are detectably labelled, and binding detection results are obtained and compared between the subject sample and the normal control sample.
A corresponding kit is also disclosed. The kit comprises a first probe that binds specifically to an exon epitope of P09493-3 and P09493-1 lacking exon 1a (SEQ ID NO:1) and a second probe that binds specifically to an exon 1a (SEQ ID NO:1) epitope, with either probe detectably labelled with a reporter moiety.
Claims Coverage
Two independent claims are present: one method claim and one kit claim. The coverage centers on distinguishing P09493-3 and/or P09493-1 isoforms using two detectably labelled probes targeting exon-specific epitopes, one excluding exon 1a and one specific for exon 1a, and comparing binding detection results with normal control samples from subjects without AD or MCI.
Exon-epitope paired antibody detection for P09493-3/P09493-1 expression in vitro
A method to determine the expression level of one or both tropomyosin isoform(s) corresponding to P09493-3 and/or P09493-1 in a sample compared to a normal control sample, comprising obtaining a sample; contacting the sample in vitro with a first antibody that binds specifically to an exon epitope of P09493-3 and P09493-1 wherein said epitope does not comprise exon 1a (SEQ ID NO:1) and a second antibody that binds specifically to an exon 1a (SEQ ID NO:1) epitope of P09493-3 and P09493-1, wherein the first and second antibodies are detectably labelled; detecting the binding of the first and second antibodies and comparing the antibody binding detection results using the sample with results using a control sample from subject(s) that do not have Alzheimer's Disease or Mild Cognitive Impairment.
Two-probe kit for exon epitope discrimination of P09493-3/P09493-1
A kit comprising a first probe that binds specifically to an exon epitope of P09493-3 and P09493-1, wherein said epitope does not comprise exon 1a (SEQ ID NO:1), and a second probe that binds specifically to an exon 1a (SEQ ID NO:1) epitope of P09493-3 and P09493-1, the first or second probes being detectably labelled with a reporter moiety.
The claim set covers an in vitro diagnostic method using paired, detectably labelled antibodies or probes that target exon epitopes distinguishing exon 1a inclusion versus exclusion for P09493-3 and P09493-1, together with a corresponding kit providing the two probes.
Stated Advantages
Provides a diagnostic approach for AD and MCI based on increased detection of P09493-3/P09493-1 expression levels.
Reported assay sensitivity is <10 ng/mL.
Reported within-run precision is <10%.
Documented Applications
In vitro diagnostic determination of expression levels of tropomyosin isoform(s) corresponding to P09493-3 and/or P09493-1 in samples for comparison between subject(s) with AD or MCI and normal control subject(s) without AD or MCI.
A kit format for detection based on probes binding exon epitopes, including exon 1a and an exon epitope lacking exon 1a, of P09493-3 and P09493-1 with detectably labelled reporter moieties.
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