Methods and compositions for diagnosis, stratification, and monitoring of alzheimer's disease and other neurological disorders in body fluids

• US 8,389,226 B2
• Filed: 02/18/2011
• Issued: 03/05/2013
• Est. Priority Date: 11/19/2003
• Status: Expired due to Fees

• Current Assignee: Rules-Based Medicine, Inc.
• Original Assignee: Rules-Based Medicine, Inc.
• Inventors: Wyss-Coray, Anton, Ray, Sandip
• Primary Examiner(s): Kolker, Daniel E
• Assistant Examiner(s): MACFARLANE, STACEY NEE
• Application Number:
  US13/031,120
• Publication Number:
  US 20110212854A1
• Time in Patent Office: 746 Days
• Field of Search: None
• US Class Current: 435/7.21
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: G01N 2800/28 Neurological disorders
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 2800/60 Complex ways of combining multiple protein biomarkers for diagnosis
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

The inventors have discovered a collection of proteinaceous biomarkers (“AD biomarkers) which can be measured in peripheral biological fluid samples to aid in the diagnosis of neurodegenerative disorders, particularly Alzheimer'"'"'s disease and mild cognitive impairment (MCI). The invention further provides methods of identifying candidate agents for the treatment of Alzheimer'"'"'s disease by testing prospective agents for activity in modulating AD biomarker levels.

Claims

1. A method of aiding diagnosis of Alzheimer'"'"'s disease (“

AD”

), comprising;

obtaining a blood sample from a human individual;

comparing normalized measured levels of a group of at least 4 AD diagnosis biomarkers from the individual'"'"'s blood sample to a reference level of each AD diagnosis biomarker;

wherein the group of AD diagnosis biomarkers comprises BDNF, PDGF-BB, Leptin and RANTES;

wherein the reference level of each AD diagnosis biomarker comprises a normalized measured level of the AD diagnosis biomarker from one or more blood samples of human individuals without AD; and

wherein levels of AD diagnosis biomarkers less than the reference level of each AD diagnosis biomarker indicate a greater likelihood that the individual suffers from AD.

2. The method of claim 1, wherein a level of BDNF decreased at least 30% compared to the reference level indicates a greater likelihood that the individual suffers from AD.

3. The method of claim 1, wherein a level of PDGF-BB decreased at least 90% compared to the reference level indicates a greater likelihood that the individual suffers from AD.

4. The method of claim 1, wherein a level of Leptin decreased at least 30% compared to the reference level indicates a greater likelihood that the individual suffers from AD.

5. The method of claim 1, wherein a level of RANTES decreased at least 15% compared to the reference level indicates a greater likelihood that the individual suffers from AD.

6. The method of claim 1, wherein a level of BDNF decreased at least 30% compared to the reference level, a level of PDGF-BB decreased at least 90% compared to the reference level, a level of Leptin decreased at least 30% compared to the reference level, and a level of RANTES decreased at least 15% compared to the reference level indicates a greater likelihood that the individual suffers from AD.