Methods for the detection of soluble amyloid .beta.-protein (.beta.AP) or soluble transthyretin (TTR)

• US 5,744,368 A
• Filed: 11/04/1993
• Issued: 04/28/1998
• Est. Priority Date: 11/04/1993
• Status: Expired due to Fees

• Current Assignee: The Research Foundation for The State University of New York (State University of New York)
• Original Assignee: The Research Foundation for The State University of New York (State University of New York)
• Inventors: Schwarzman, Alexander L., Eisenberg-Grunberg, Moises, Goldgaber, Dmitry Y.
• Primary Examiner(s): Adams, Donald E.
• Assistant Examiner(s): DUFFY, PATRICIA ANN
• Application Number:
  US08/148,117
• Time in Patent Office: 1,636 Days
• Field of Search: 436/501, 436/504, 436/503, 436/518, 436/528, 436/531, 436/804, 435/7.93, 435/7.8, 435/7.9
• US Class Current: 436/501
• CPC Class Codes: C07K 14/4711 Alzheimer's disease; Amyloid plaque core protein
• CPC Class Codes: C07K 14/76 Albumins
• CPC Class Codes: C07K 14/775 Apolipopeptides
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease
• CPC Class Codes: Y10S 436/804 Radioisotope, e.g. radioimmunoassay

Abstract

This invention is directed to methods and compositions for preventing aggregation of amyloid β-protein (βAP) aggregation. Aggregation of amyloid β-protein is associated with the deposition of amyloid in the brain. Amyloid β-protein-binding compounds such as transthyretin are described which form complexes with βAP and prevent formation of amyloid. This invention also identifies the serine 6 mutation in the TTR gene as predictive of person at risk for developing βAP associated amyloidosis.

Claims

1. An in vitro method to detect the ability of a soluble transthyretin (TTR) present in a sample, to specifically bind soluble amyloid β

protein (β

AP), said method comprising;

(a) contacting the sample containing the soluble TTR with β

AP to form a transthyretin (TTR)/β

AP complex, and;

(b) detecting said complex wherein the presence of said complex indicates the ability of the soluble TTR to specifically bind β

AP.

2. The method according to claim 1 wherein the sample is CSF.

3. The method according to claim 1 wherein the β

AP is bound to a solid support.

4. An in vitro method to detect the ability of a soluble transthyretin (TTR) present in a sample, to specifically bind a soluble amyloid β

protein (β

AP), said method comprising;

(a) forming a complex comprising a labelled TTR specifically bound to the β

AP; and

(b) contacting the sample suspected of containing soluble TTR with said complex; and

(c) detecting the displacement of said labelled TTR from said complex wherein the displacement of said labelled TTR from said complex indicates the presence of soluble TTR in the sample.

5. The method according to claim 4 wherein said β

AP is bound to a solid support.

6. An in vitro method to detect soluble amyloid β

protein (β

AP) in a sample, said method comprises;

(a) forming a complex comprising a labelled ligand specifically bound to a transthyretin (TTR); and

(b) contacting the sample suspected of containing soluble β

AP with said complex; and

(c) detecting the displacement of said labelled ligand from said complex wherein the displacement of labelled ligand from the TTR indicates the presence of soluble β

AP in the sample.

7. The method according to claim 6 wherein TTR is bound to a solid support and the labelled ligand is a predetermined amount of β

AP.

8. An in vitro method to detect the ability of a soluble amyloid β

-protein (β

AP) present in a sample, to specifically bind a transthyretin (TTR), said method comprising;

(a) contacting the sample containing the β

AP with the TTR to form a transthyretin (TTR)/β

AP complex, and;

(b) detecting said complex wherein the presence of said complex indicates the ability of the soluble β

AP to specifically bind TTR.

9. The method according to claim 8, wherein the TTR is bound to a solid support.