# US 11,299,555 B2 · Method for diagnosing alzheimer's disease using signal peptide as indicator

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- Number: US 11,299,555 B2
- Document ID: US11299555B2
- Status: Granted
- Kind: B2
- Application number: 16/081,189
- Filed: 2017-03-02
- Published: 2019-03-07
- Granted: 2022-04-12
- Earliest claimed: 2016-03-03
- Assignees: Toagosei Co., Ltd.; National University Corporation Nagoya University
- Applicants: Toagosei Co., Ltd.; National University Corporation Nagoya University
- Inventors: Nahoko Baileykobayashi; Makoto Sawada; Tetsuhiko Yoshida
- Web page: https://patentgrep.com/patent/US11299555B2

## CPC

- C07K 17/08: the carrier being a synthetic polymer
- G01N 33/6851: {Methods of protein analysis involving laser desorption ionisation mass spectrometry}
- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- C07K 14/47: from mammals
- G01N 2800/2821: Alzheimer
- G01N 2800/60: Complex ways of combining multiple protein biomarkers for diagnosis
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

This method for aiding Alzheimer's detection provided by the present invention includes: determining a profile of signal peptides contained in a bodily fluid from a test subject, and comparing the signal peptide profile thus determined for the test subject with a previously-determined profile of signal peptides in a bodily fluid from a healthy subject. A difference between the signal peptide profile of the test subject and the signal peptide profile of the healthy subject at a specific molecular weight is then associated with the test subject's suffering from or developing Alzheimer's.

## Claims

### Claim 1

A method for aiding detection of Alzheimer's disease, the method comprising:
analyzing to determine a presence or absence of an Alzheimer's-associated signal peptide or analyzing to determine a degree of abundance of the Alzheimer's-associated signal peptide when the Alzheimer's-associated signal peptide is present in a bodily fluid from a test subject, and
comparing the presence or absence of the Alzheimer's-associated signal peptide or the degree of abundance of the Alzheimer's-associated signal peptide in the bodily fluid from the test subject with a reference level set based on results obtained by analyzing the presence or absence of the Alzheimer's-associated signal peptide or the degree of abundance of the Alzheimer's-associated signal peptide in a bodily fluid from at least one healthy subject, wherein
a molecular weight of the Alzheimer's-associated signal peptide is: 1629.17±2, 1767.38±2, 1900.43±2, 1933.29±2, 1966.96±2 1996.12±2, 2187.30±2, 2196.08±2, 2196.64±2, or 2240.20±2, wherein
an amino acid sequence constituting the Alzheimer's-associated signal peptide is any of the amino acid sequences represented by SEQ ID NOS: 1 to 75;
and wherein analyzing to determine the presence or absence of the Alzheimer's-associated signal peptide or to determine the degree of abundance of the Alzheimer's-associated signal peptide in the bodily fluid from the test subject comprises testing with a mass spectrometer and
immobilizing the bodily fluid on a thermoplastic resin before the presence or absence of the Alzheimer's-associated signal peptide or the degree of abundance of the Alzheimer's-associated signal peptide in the bodily fluid is tested, wherein the presence or absence of the Alzheimer's-associated signal peptide or the degree of abundance of the Alzheimer's-associated signal peptide in the bodily fluid immobilized on the thermoplastic resin is determined by testing with a matrix assisted laser desorption/ionization-time-of-flight mass spectrometry.

### Claim 2 (depends on 1)

The method according to claim 1, wherein at least 10 kinds of Alzheimer's-associated signal peptides with molecular weights differing by at least 3 from each other are tested for the bodily fluid from the test subject.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the bodily fluid is cerebrospinal fluid.