Biomarkers for cognitive impairment and methods for detecting cognitive impairment using such biomarkers
Inventors
Uchida, Kazuhiko • 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-11307208-B2
Publication Date
2022-04-19
Expiration Date
Abstract
The present invention aims to provide methods to detect cognitive impairment including mild cognitive impairment and Alzheimer disease by using a protein or its partial peptide that differs in presence or absence, or in quantity between non-cognitive impairment and patients with cognitive impairment and further aims to present biomarkers comprising said protein and said partial peptide to be used to detect cognitive impairment including Alzheimer disease or mild cognitive impairment. Specifically, a biomarker for diagnosis of psychiatry disease or cognitive impairment comprising 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 amino acid sequence expressed by SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, and 25 and selected from the group of partial peptide in these proteins consisting of amino acid sequence expressed by SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, and 27. And further aims to provide diagnostic method using these biomarker.
Core Innovation
The disclosure relates to biomarker proteins and specific blood/serum-associated protein fragments and peptides, including up to 55-aa protein fragments derived from proteins identified by SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and peptide fragments SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 27. These biomarker peptides are used for detecting cognitive impairment, including Alzheimer disease and mild cognitive impairment.
The document provides diagnostic methods that detect and/or quantify the biomarkers in biological materials, including serum, using techniques such as 2D-LC-MALDI-TOF/TOF mass spectrometry and immunoMS. A set of marker peptides is reported with statistical performance using differential abundance and ROC/AUC values, including CO3 (SEQ ID NO:2) and THRB (SEQ ID NO:14), to distinguish Alzheimer disease and mild cognitive impairment from non-demented control.
The disclosed diagnostic approach is grounded on comparing a detected amount of a specific biomarker peptide to an amount measured in a non-psychiatry disease subject, and then using the comparison outcome for diagnosis among Alzheimer disease, mild cognitive impairment, Dementia with Lewy bodies, or frontotemporal dementia. The method is further linked to administering an effective amount of an anti-acetylcholinesterase inhibitor to the diagnosed patient.
Claims Coverage
The independent claim provides a diagnostic and treatment method with two primary inventive features: detecting Prothrombin-derived peptide THRB (SEQ NO: 14) by mass spectrometry and administering an anti-acetylcholinesterase inhibitor after diagnosis.
Prothrombin-derived peptide THRB detection by mass spectrometry for dementia diagnosis
Detecting an amount of Prothrombin-derived peptide THRB consisting of SEQ NO: 14 in a biological material sample by mass spectrometry, and diagnosing when a higher amount is detected by comparing the amount in the patient with an amount in a non-psychiatry disease subject.
Anti-acetylcholinesterase inhibitor administration after diagnosis
Administering an effective amount of an anti-acetylcholine esterase inhibitor to the diagnosed patient.
Overall, the claim coverage centers on diagnosing Alzheimer disease, mild cognitive impairment, Dementia with Lewy bodies, or frontotemporal dementia using mass spectrometry detection of Prothrombin-derived peptide THRB (SEQ ID NO: 14), followed by administering an effective anti-acetylcholinesterase inhibitor upon diagnosis.
Stated Advantages
Enables diagnosing Alzheimer disease, mild cognitive impairment, Dementia with Lewy bodies, or frontotemporal dementia based on detecting a higher amount of Prothrombin-derived peptide THRB (SEQ ID NO: 14) compared with a non-psychiatry disease subject.
Documented Applications
Diagnosing cognitive impairment conditions including Alzheimer disease, mild cognitive impairment, Dementia with Lewy bodies, and frontotemporal dementia in a patient using detection of Prothrombin-derived peptide THRB (SEQ ID NO: 14) by mass spectrometry.
Supporting the administration of an anti-acetylcholinesterase inhibitor after diagnosis of the specified dementias and mild cognitive impairment.
Providing diagnostic kits for detection of the biomarker peptides in biological materials, including utility for judging drug efficacy.
Interested in licensing this patent?