Methods for diagnosing neurodegenerative diseases

Abstract

The present invention relates to an in vitro method for diagnosing or predicting neurodegenerative diseases in a subject, the method comprising A / T / N classification of a nasal secretion sample obtained from the subject. The A / T / N classification may, but is not limited to, be used for diagnosing Alzheimer's disease (AD), diagnosing SNAP, or excluding AD.

Claims

1. An in vitro method for diagnosing or predicting neurodegenerative diseases in a subject, comprising A / T / N classification of nasal secretion samples obtained from the subject.

2. The following steps (a) to (e): a) In the nasal secretion sample obtained from the subject, i) Protein-specific biomarker signatures (multiple signatures are possible) for beta-amyloid. ii) Protein-specific biomarker signatures(s) of phosphorylated tau, and / or iii) Protein-specific biomarker signatures (multiple signatures allowed) for total tau. The process of determining; b) A step of determining classification-specific scores for A, T, and / or N from the protein-specific biomarker signature(s) determined in a); c) A step of comparing the classification-specific score determined in b) with a pre-determined classification-specific score; d) Target i) According to the comparison results of the classification-specific scores for A determined in c), A+ or A-, In accordance with the comparison results of the classification-specific scores for T determined in ii) c), T+ or T-, and / or According to the comparison results of the classification-specific scores for n determined in iii) c), N+ or N-, The process of classifying; e) A step of diagnosing or predicting neurodegenerative diseases based on the classification in d), The method according to claim 1, including the method described in claim 1.

3. The method according to claim 2, wherein the protein-specific biomarker signature(s) of a) includes the total protein level of beta-amyloid, phosphorylated tau and / or total tau, and / or the protein level of the quaternary structure and / or isoform of beta-amyloid, phosphorylated tau and total tau.

4. The method according to claim 3, wherein the protein level is determined by a technique that includes separating the quaternary structure and / or isoforms according to size, molecular weight, or charge.

5. The method according to claim 4, wherein the technique is electrophoresis.

6. The method according to any one of claims 1 to 5, wherein the quaternary structure and / or isoforms are separated between about 2 kDa and about 440 kDa.

7. The method according to any one of claims 1 to 6, wherein the isoform of beta-amyloid is Aβ40 and / or Aβ42.

8. The method according to any one of claims 1 to 7, wherein the quaternary structure of the beta-amyloid has a molecular weight of approximately 4 kDa, approximately 8 kDa, approximately 12 kDa, approximately 16 kDa, approximately 19 kDa, approximately 24 kDa, approximately 32 kDa, approximately 40 kDa, approximately 44 kDa, approximately 48 kDa, approximately 52 kDa, approximately 56 kDa, approximately 60 kDa to 72 kDa, approximately 84 to 120 kDa, and / or a molecular weight greater than approximately 140 kDa.

9. The method according to any one of claims 1 to 8, wherein the quaternary structure of phosphorylated tau has molecular weights of approximately 30 kDa, approximately 38 kDa, approximately 55 kDa to 62 kDa, approximately 96 kDa to 106 kDa, and approximately 140 to 160 kDa.

10. The method according to any one of claims 1 to 9, wherein the quaternary structure of total tau has molecular weights of approximately 30 kDa, approximately 38 kDa, approximately 48 kDa, approximately 55 kDa to 62 kDa, approximately 96 kDa to 106, approximately 140 kDa to 160 kDa, and molecular weights greater than 160 kDa.

11. The determination of classification-specific scores is i) Total protein levels of beta-amyloid, phosphorylated tau, and / or total tau; ii) Protein(s) of the quaternary structures and / or isoforms of beta-amyloid, phosphorylated tau, and / or total tau; iii) The ratio of total protein levels of beta-amyloid, phosphorylated tau, and / or total tau; iv) The ratio of the total protein level(s) of beta-amyloid, phosphorylated tau, and / or total tau to the protein level(s) of the quaternary structure(s) and / or isoform(s) of beta-amyloid, phosphorylated tau, and / or total tau; v) The ratio of the protein levels of the quaternary structures and / or isoforms of beta-amyloid, phosphorylated tau and / or total tau to the total protein levels of beta-amyloid, phosphorylated tau and / or total tau; and / or vi) The ratio of the protein levels of different quaternary structures and / or isoforms of beta-amyloid, phosphorylated tau, and / or total tau to the protein levels of beta-amyloid, phosphorylated tau, and / or total tau, The method according to any one of claims 1 to 10, including the method described in any one of claims 1 to 10.

12. The method according to any one of claims 1 to 11, wherein the determination of a classification-specific score includes applying logistic regression fitting, neural networks, ensemble learning, dimensionality reduction techniques, and / or Bayesian classifiers to protein-specific biomarker signatures.

13. The method according to any one of claims 1 to 12, wherein step c) is to compare the classification-specific score with a predetermined cutoff.

14. The method according to any one of claims 1 to 13, wherein the nasal secretion sample is obtained from one or both of the olfactory clefts of the subject.

15. The method according to any one of claims 1 to 14, further comprising options for the treatment of neurodegenerative diseases.

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