Biomarker for mental disorders including cognitive disorders, and method using said biomarker to detect mental disorders including cognitive disorders
Inventors
Uchida, Kazuhiko • Ishi, Takashi • Meno, Kohji • Suzuki, Hideaki
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11726099-B2
Publication Date
2023-08-15
Expiration Date
Abstract
Methods are provided that detect cognitive impairment including mild cognitive impairment and Alzheimer disease by using a protein or its partial peptide that differs in presence or absence. Novel biomarkers are also provided for cognitive impairment and non-psychiatric disease, as well as methods for detecting cognitive impairment using such biomarkers. Specifically, a biomarker for diagnosis is provided that comprises a protein fragment or peptide of not less than 5 amino acid residues arising from at least one protein or peptide selected from the group of proteins consisting of an amino acid sequence expressed by SEQ ID NO: 1, 3, 6, 8, 10, 13, 15, 18, or 20 and selected from the group of partial peptide in these proteins consisting of an amino acid sequence expressed by SEQ ID NO: 2, 4, 5, 7, 9, 11, 12, 14, 16, 17, 19, or 21.
Core Innovation
The invention relates to serum biomarkers for cognitive impairment, including mild cognitive impairment (MCI) and Alzheimer’s disease (AD), and also certain psychiatric/non-demented neurological disorders. Biomarkers are described as protein fragments/peptides with lengths of no more than 5 residues, derived from multiple source proteins, including prothrombin precursor-derived peptides THRB(R−) and THRB(R+) and a neurexin-2-beta precursor-derived peptide NRX2B.
A central concept is the detection of objective peptide markers in blood-serum to support diagnosis at a preclinical stage, contrasting prior subjective or expensive diagnostic approaches. The document describes measuring peptide biomarkers in an acid-treated serum sample or an ultrafiltered sample after acid-treatment, and diagnosis based on levels of specific peptides, including the absence or decrease of THRB(R−) and the presence or increase of THRB(R+) in comparison to biological material of subjects not suffering from MCI or AD.
The document further describes workflows for detecting and verifying peptide biomarkers, including mass-spectrometry approaches such as 2D-LC-MALDI TOF-MS and LC-MS/MS, as well as immunoMS using antibody-based capture. Example results are reported using differential abundance and ROC-based performance evaluation for marker peptides, and verification is described using immunoMS with stable isotope-labeled peptide spiking to confirm identity. The disclosure also indicates utility for kits/systems and potential use for drug efficacy assessment.
Claims Coverage
The independent claim covers a preclinical serum-biomarker detection and diagnosis method for mild cognitive impairment or Alzheimer’s disease in a human subject, with diagnosis triggered by specific presence/decrease patterns of prothrombin precursor-derived peptides THRB(R−) and THRB(R+), and measurement performed with either 2D-LC-MALDI TOF-MS or LC-MS/MS on an acid-treated or ultrafiltered-after-acid serum sample.
Preclinical serum sample biomarker detection for MCI/AD
Obtaining a serum sample from a human subject at a preclinical stage and measuring at least one biomarker in the serum sample, wherein the at least one biomarker is a peptide selected from prothrombin precursor-derived peptide THRB(R−) and prothrombin precursor-derived peptide THRB(R+).
Mass-spectrometry detection using acid-treated or ultrafiltered-after-acid serum
Measuring the at least one biomarker using a detection method selected from 2D-LC-MALDI TOF-MS and LC-MS/MS, wherein the serum sample is an acid-treated sample or an ultrafiltered sample after acid-treatment.
Diagnosis based on THRB(R−) absence/decrease and THRB(R+) presence/increase
Diagnosing the human subject with mild cognitive impairment or Alzheimer’s disease based on the level of the at least one biomarker if THRB(R−) is absent or decreased in the serum sample and/or if THRB(R+) is present or increased in the serum sample as compared to biological material of subjects not suffering from MCI or AD.
Overall, the claim set focuses on preclinical diagnosis of MCI/AD by serum peptide measurement, specifically leveraging THRB(R−) and THRB(R+), measured by 2D-LC-MALDI TOF-MS or LC-MS/MS from acid-treated or ultrafiltered-after-acid serum, with diagnosis criteria tied to peptide absence/decrease versus presence/increase.
Stated Advantages
Supports diagnosis at a preclinical stage.
Contrasts with prior subjective or expensive diagnostic approaches.
Provides objective peptide markers in blood-serum.
Documented Applications
Diagnosis of mild cognitive impairment (MCI).
Diagnosis of Alzheimer’s disease (AD).
Certain psychiatric/non-demented neurological disorders.
Potential use for drug efficacy assessment.
Kits/systems for peptide biomarker detection.
Interested in licensing this patent?