US4666829A
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Polypeptide marker for Alzheimer's disease and its use for diagnosis
Assignee: University of California
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Filing: 1985-05-15
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Granted: 1987-05-19
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Expires: 2005-05-15
Abstract
Abstract A novel polypeptide, Alzheimer's Amyloid Polypeptide (AAP), is provided in substantially purified form which is isolated from amyloid deposits in patients with Alzheimer's Disease. The polypeptide has the following amino acid sequence: H2N-ASP-ALA-GLU-PHE-ARG-HIS-ASP- -SER-GLY-TYR-GLN-VAL-HIS-HIS-GLN- -LYS-LEU-VAL-PHE-PHE-ALA-GLU-ASP- +TR -VAL-GLY-SER-ASN-LYS-COOH. The polypeptide, or fragments thereof, may be used to produce antibodies useful in a diagnostic test for Alzheimer's Disease. Nucleotide probes corresponding to portions of the polypeptide are also useful for diagnostic purposes.
Inventors
- 👤 George G. Glenner
- 👤 Caine W. Wong
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 19:31
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/68; G01N33/6893; G01N33/6896; C; C07; C07K; C07K14/00; C07K14/435; C07K14/46; C07K14/47; C07K14/4701; C07K14/4711; C12; C12Q; C12Q1/00; C12Q1/68; C12Q1/6876; C12Q1/6883; G01N2474/00; G01N2474/20; G01N2800/00; G01N2800/28; G01N2800/2814; G01N2800/2821; Y; Y10; Y10S; Y10S435/00; Y10S435/961; Y10S530/00; Y10S530/806
Claims Analysis
Total Claims: 47
Claim 1
Independent Claim
20 words
A substantially purified polypeptide isolated from patients with Alzheimer's Disease, Alzheimer's Amyloid Polypeptide, having the following amino acid sequence: ##STR6##
Claim 2
Dependent Claim
20 words
A substantially purified polypeptide isolated from patients with Alzheimer's Disease, Alzheimer's Amyloid Polypeptide, having the following amino acid sequence: ##STR6##
Claim 3
Dependent Claim
16 words
A composition comprising the substantially purified polypeptide of claim 1, solubilized in a basic guanidine solution.
Claim 4
Dependent Claim
24 words
A composition comprising the substantially purified polypeptide of claim 2, wherein the basic guanidine solution is 6M guanidine-HCl, having a pH of about 8.0.
Claim 5
Dependent Claim
46 words
A reagent for use in the diagnosis of Alzheimer's Disease in a human patient, comprising antibodies obtained by means of an immune response to exposure to the substantially purified polypeptide isolated from patients with Alzheimer's Disease, Alzheimer's Amyloid Polypeptide, having the following amino acid sequence: ##STR7##
Claim 6
Dependent Claim
46 words
A reagent for use in the diagnosis of Alzheimer's Disease in a human patient, comprising antibodies obtained by means of an immune response to exposure to the substantially purified polypeptide isolated from patients with Alzheimer's Disease, Alzheimer's Amyloid Polypeptide, having the following amino acid sequence: ##STR7##
Claim 7
Dependent Claim
11 words
The diagnostic reagent of claim 4, wherein the antibodies are polyclonal.
Claim 8
Dependent Claim
25 words
The diagnostic reagent of claim 4 wherein the immune response is produced in a mammal selected from the group consisting of rabbits, goats and mice.
Claim 9
Dependent Claim
11 words
The diagnostic reagent of claim 4 wherein the antibodies are monoclonal.
Claim 10
Dependent Claim
16 words
The diagnostic reagent of claim 4 wherein the immune response is produced in murine-murine hybridoma cells.
Claim 11
Dependent Claim
93 words
A diagnostic method for determining the presence of Alzheimer's Disease in a human patient by detecting the presence of Alzheimer's Amyloid Polypeptide in the patient through an immunoassay, comprising the steps of: a. combining a sample of the human patient's body fluid suspected of containing Alzheimer's Amyloid Polypeptide with antibodies specific to Alzheimer's Amyloid Polypeptide, having the following amino acid sequence: ##STR8## b. monitoring the combination of step a. to determine whether said antibodies have bound to said Alzheimer's Amyloid Polypeptide in an immunological reaction, thereby indicating that said patient has Alzheimer's Disease.
Claim 12
Dependent Claim
93 words
A diagnostic method for determining the presence of Alzheimer's Disease in a human patient by detecting the presence of Alzheimer's Amyloid Polypeptide in the patient through an immunoassay, comprising the steps of: a. combining a sample of the human patient's body fluid suspected of containing Alzheimer's Amyloid Polypeptide with antibodies specific to Alzheimer's Amyloid Polypeptide, having the following amino acid sequence: ##STR8## b. monitoring the combination of step a. to determine whether said antibodies have bound to said Alzheimer's Amyloid Polypeptide in an immunological reaction, thereby indicating that said patient has Alzheimer's Disease.
Claim 13
Dependent Claim
28 words
The diagnostic method of claim 9, wherein said combining step further includes adding a known quantity of labelled Alzheimer's Amyloid Polypeptide, whereby a competitive immunoassay is established .
Claim 14
Dependent Claim
14 words
The diagnostic method of claim 10, wherein said label is capable of emitting radiation.
Claim 15
Dependent Claim
12 words
The diagnostic method of claim 11, wherein said label is 125 I.
Claim 16
Dependent Claim
79 words
A diagnostic method for determining the presence of Alzheimer's Disease in a human patient by histological localization of Alzheimer's Amyloid Polypeptide, comprising the steps of: a. combining a sample of the human patient's tissue with antibodies specific to Alzheimer's Amyloid Polypeptide, having the following amino acid sequence: ##STR9## b. monitoring the combination of step a. to determine whether said antibodies have bound to said Alzheimer's Amyloid Polypeptide in an immunological reaction, thereby indicating that said patient has Alzheimer's Disease.
Claim 17
Dependent Claim
79 words
A diagnostic method for determining the presence of Alzheimer's Disease in a human patient by histological localization of Alzheimer's Amyloid Polypeptide, comprising the steps of: a. combining a sample of the human patient's tissue with antibodies specific to Alzheimer's Amyloid Polypeptide, having the following amino acid sequence: ##STR9## b. monitoring the combination of step a. to determine whether said antibodies have bound to said Alzheimer's Amyloid Polypeptide in an immunological reaction, thereby indicating that said patient has Alzheimer's Disease.
Claim 18
Dependent Claim
27 words
The diagnostic method of claim 13, wherein said combining step further includes adding a known quantity of labelled Alzheimer's Amyloid Polypeptide, whereby a competitive immunoassay is established.
Claim 19
Dependent Claim
14 words
The diagnostic method of claim 13, wherein said label is capable of emitting radiation.
Claim 20
Dependent Claim
12 words
The diagnostic method of claim 13, wherein said label is 125 I.
Claim 21
Dependent Claim
16 words
The diagnostic method of claim 14, wherein said label is a component of an enzymatic reaction.
Claim 22
Dependent Claim
38 words
A labelled nucleotide probe, comprising a sequence of nucleic acid substantially complementary to the nucleotide sequence coding for the substantially purified polypeptide isolated from patients with Alzheimer's Disease, Alzheimer's Amyloid Polypeptide, having the following amino acid sequence: ##STR10##
Claim 23
Dependent Claim
38 words
A labelled nucleotide probe, comprising a sequence of nucleic acid substantially complementary to the nucleotide sequence coding for the substantially purified polypeptide isolated from patients with Alzheimer's Disease, Alzheimer's Amyloid Polypeptide, having the following amino acid sequence: ##STR10##
Claim 24
Dependent Claim
16 words
The nucleotide probe of claim 18, wherein the nucleotide sequence coding for said polypeptide is DNA.
Claim 25
Dependent Claim
82 words
A method of detecting individuals possessing a nucleotide sequence coding for the polypeptide of claim 1, comprising the steps of: a. providing a labelled nucleotide probe capable of selectively hybridizing with a portion of the nucleotide sequence coding for the substantially purified polypeptide isolated from patients with Alzheimer's Disease, Alzheimer's Amyloid Polypeptide, having the following amino acid sequence: ##STR11## b. exposing the nucleotide probe to a tissue sample from a patient; c. monitoring the reaction of step b. for nucleic acid hybridization.
Claim 26
Dependent Claim
22 words
The method of claim 20, wherein said label is selected from the group consisting of 32 P, 3 H, and 14 C.
Claim 27
Dependent Claim
55 words
An immunogenic peptide fragment of a substantially purified polypeptide isolated from patients with Alzheimer's Disease, Alzheimer's Amyloid Polypeptide, comprising: a linear sequence of amino acids corresponding to any subsequence of the following amino acid sequence: ##STR12## said linear sequence being immunogenic so as to induce the production of active antibodies specific to Alzheimer's Amyloid Polypeptide.
Claim 28
Dependent Claim
55 words
An immunogenic peptide fragment of a substantially purified polypeptide isolated from patients with Alzheimer's Disease, Alzheimer's Amyloid Polypeptide, comprising: a linear sequence of amino acids corresponding to any subsequence of the following amino acid sequence: ##STR12## said linear sequence being immunogenic so as to induce the production of active antibodies specific to Alzheimer's Amyloid Polypeptide.
Claim 29
Dependent Claim
33 words
An immunogenic peptide fragment of substantially purified polypeptide isolated from patients with Alzheimer's Disease, Alzheimer's Amyloid Polypeptide, as recited in claim 22, wherein the peptide fragment is about 10 amino acids in length.
Claim 30
Dependent Claim
35 words
An immunogenic peptide fragment of a substantially purified polypeptide isolated from patients with Alzheimer's Disease, Alzheimer's Amyloid Polypeptide, as recited in claim 23, within the linear sequence of amino acids is as follows: H.sub.2 N-ASP-ALA-GLU-PHE-ARG-HIS-ASP-SER-GLY-TYR-COOH.
Claim 31
Dependent Claim
31 words
A composition comprising the peptide fragment of a substantially purified polypeptide isolated from patients with Alzheimer's Disease, Alzheimer's Amyloid Polypeptide, as recited in claim 22, solubilized in a basic guanidine solution.
Claim 32
Dependent Claim
30 words
A composition comprising the peptide fragment of a substantially purified polypeptide isolated from patients with Alzheimer's Disease, Alzheimer's Amyloid Polypeptide, as recited in claim 22, coupled to an immunogenic carrier.
Claim 33
Dependent Claim
34 words
A reagent for use in the diagnosis of Alzheimer's Disease in a human patient, comprising antibodies obtained by means of an immune response to exposure to the peptide fragment as recited in claim 22.
Claim 34
Dependent Claim
11 words
The diagnostic reagent of claim 27, wherein the antibodies are polyclonal.
Claim 35
Dependent Claim
25 words
The diagnostic reagent of claim 27 wherein the immune response is produced in a mammal selected from the group consisting of rabbits, goats and mice.
Claim 36
Dependent Claim
11 words
The diagnostic reagent of claim 27, wherein the antibodies are monoclonal.
Claim 37
Dependent Claim
16 words
The diagnostic reagent of claim 27, wherein the immune response is produced in murine-murine hybridoma cells.
Claim 38
Dependent Claim
78 words
A diagnostic method for determining the presence of Alzheimer's Disease in a human patient, comprising the steps of: a. combining a sample of body fluid from the patient with the antibodies obtained by means of an immune response to a peptide fragment as recited in claim 22 b. monitoring the combination of step a. to determine whether said antibodies have bound to said Alzheimer's Amyloid Polypeptide in an immunological reaction, thereby indicating that said patient has Alzheimer's Disease.
Claim 39
Dependent Claim
31 words
The diagnostic method of claim 32, wherein said combining step further includes adding a known quantity of the peptide fragment as recited in claim 32, which peptide fragment has been labelled.
Claim 40
Dependent Claim
14 words
The diagnostic method of claim 33, wherein said label is capable of emitting radiation.
Claim 41
Dependent Claim
12 words
The diagnostic method of claim 34, wherein said label is 125 I.
Claim 42
Dependent Claim
16 words
The diagnostic method of claim 33, wherein said label is a component of an enzymatic reaction.
Claim 43
Dependent Claim
89 words
A diagnostic method for determining the presence of Alzheimer's Disease in a human patient by detecting the presence of Alzheimer's Amyloid Polypeptide in the patient through an immunoassay, comprising the steps of: a. combining a sample of the patient's tissue suspected of containing Alzheimer's Amyloid Polypeptide with antibodies specific to a peptide fragment as recited in claim 22 b. monitoring the combination of step a. to determine whether said antibodies have bound to said Alzheimer's Amyloid Polypeptide in an immunological reaction, thereby indicating that said patient has Alzheimer's Disease.
Claim 44
Dependent Claim
31 words
The diagnostic method of claim 37, wherein said combining step further includes adding a known quantity of the immunogenic peptide fragment recited in claim 22, whereby a competitive immunoassay is established.
Claim 45
Dependent Claim
14 words
The diagnostic method of claim 38, wherein said label is capable of emitting radiation.
Claim 46
Dependent Claim
12 words
The diagnostic method of claim 39, wherein said label is 125 I.
Claim 47
Dependent Claim
16 words
The diagnostic method of claim 38, wherein said label is a component of an enzymatic reaction.
References Cited (Backward Citations)
No citation records indexed.
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