Biomarker for cognitive dysfunction disease and method for detecting cognitive dysfunction disease using biomarker
Inventors
Uchida, Kazuhiko • Meno, Kohji • Suzuki, Hideaki
Assignees
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Publication Number
US-11543418-B2
Publication Date
2023-01-03
Expiration Date
Abstract
This invention provides a method for detecting cognitive disfunction diseases including mild cognitive impairment and Alzheimer's disease using a protein and a peptide of the protein different in the presence level in subjects having a normal cognitive function and patients suffering from cognitive disfunction diseases and a biomarker for detecting cognitive disfunction diseases including mild cognitive impairment and Alzheimer's disease containing the protein and the peptide. This invention is a biomarker for diagnosing cognitive disfunction diseases containing a prothrombin precursor protein of SEQ ID NO: 1 or a peptide THRB containing the amino acid sequence represented by SEQ ID NO: 2 which is a peptide of the protein, a diagnosis method for cognitive disfunction diseases using the biomarker, an antigen peptide represented by SEQ ID NO: 3 for creating a THRB peptide specific antibody to be used in the diagnosis method, and a cognitive disfunction disease diagnosis kit containing the THRB peptide specific antibody.
Core Innovation
The patent discloses a biomarker and diagnostic approach for cognitive dysfunction diseases, focusing on mild cognitive impairment and Alzheimer’s disease. The approach centers on a prothrombin precursor-derived peptide identified as THRB (SEQ ID NO: 2, TATSEYQTFFNPR), including variants with 1–3 amino acid modifications. The disclosed diagnostic workflow uses subject-derived biological samples and detects the peptide corresponding to SEQ ID NO: 2 as a marker associated with the cognitive dysfunction disease.
The disclosed method includes preparing a biological sample extracted from the subject, processing the biological sample with acid treatment, and processing the acid-treated biological sample by ultrafiltration. The peptide consisting of the amino acid sequence represented by SEQ ID NO: 2 is detected using a mass spectrometry method or an immuno-MS method, and the mass spectrometry method is 2D-LC-MALDI TOF-MS or LC-MS/MS. A positive detecting result is used to diagnose mild cognitive impairment or Alzheimer’s disease.
The disclosed diagnostic approach also includes a comparative format in which a separate subject having the cognitive dysfunction disease provides a first biological sample, and a second biological sample is extracted from the subject to be diagnosed. Both samples are subjected to the same acid treatment and ultrafiltration processing, and the amount of the peptide represented by SEQ ID NO: 2 is measured by mass spectrometry or immuno-MS. Diagnosis is made based on whether the comparison shows no statistical difference between the measured amounts in the two samples.
Claims Coverage
The partial document provides two independent claims. Both claims share a common inventive core: detection or measurement of the THRB peptide defined by SEQ ID NO: 2 after acid treatment and ultrafiltration, using mass spectrometry or immuno-MS, for diagnosing mild cognitive impairment or Alzheimer’s disease.
Peptide-SEQ ID NO: 2 detection after acid treatment and ultrafiltration with mass spectrometry or immuno-MS
A method for diagnosing mild cognitive impairment or Alzheimer's disease in a subject that comprises preparing a biological sample extracted from the subject, processing the biological sample with acid treatment, processing the acid-treated biological sample by ultrafiltration, and detecting a peptide consisting of an amino acid sequence represented by SEQ ID NO: 2 in the biological sample by a mass spectrometry method or an immuno-MS method; wherein the mass spectrometry method is a 2D-LC-MALDI TOF-MS method or LC-MS/MS method and diagnosing is performed when a positive detecting is obtained.
Comparative measurement of peptide-SEQ ID NO: 2 between diseased and test samples
A method for diagnosing mild cognitive impairment or Alzheimer's disease in a subject that comprises providing a separate subject having the cognitive dysfunction disease; preparing a first biological sample extracted from the separate subject having the cognitive dysfunction disease and preparing a second biological sample extracted from the subject to be diagnosed; processing the first and second biological samples respectively with acid treatment and processing the acid-treated first and second biological samples respectively by ultrafiltration; measuring the amount of a peptide consisting of an amino acid sequence represented by SEQ ID NO: 2 in both biological samples by a mass spectrometry method or an immuno-MS method; and diagnosing the subject when, by comparing the measured amount from the first biological sample with that from the second biological sample, there is no statistical difference between the two; wherein the mass spectrometry method is a 2D-LC-MALDI TOF-MS method or LC-MS/MS method.
Across both independent claims, the key claimed concept is diagnosing mild cognitive impairment or Alzheimer’s disease by detecting or measuring the THRB peptide corresponding to SEQ ID NO: 2 in subject-derived biological samples after acid treatment and ultrafiltration, using either mass spectrometry or an immuno-MS method, with either a positive detection or a no-statistical-difference comparison serving as the diagnostic criterion.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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