Biomarkers Consortium - Plasma Aβ as a Predictor of Amyloid Positivity in Alzheimer's Disease

Transforming the ability to treat Alzheimer’s disease by enabling early and reliable diagnosis

The Problem
Early treatment of Alzheimer’s disease requires early diagnosis. Yet available methods to diagnose early AD are expensive or invasive, and traditional diagnostic methods based on symptoms cannot detect early disease.
The Solution
This project will accelerate the development of cost-effective and noninvasive tools to diagnose early AD, supporting early intervention and improved treatments for patients.

Overview

A recently proposed research framework further defines patients affected by Alzheimer’s disease (AD) based on pathological hallmarks – especially levels of amyloid (Aβ) and tau, and neurodegeneration status (A/T/N) – not just based on symptoms or signs such as mild cognitive impairment (MCI). This research framework is intended to guide drug development studies by diagnosing AD with biomarkers at the earliest stages before the onset of symptoms (pre-symptomatic).  

Currently, amyloid status can only be assessed by PET imaging of Aβ or by cerebral spinal fluid (CSF) Aβ measurements, which are extremely costly (PET) or require invasive procedures (CSF lumbar puncture). These procedures, and the aspiration to define patients by the pathological criteria described above, are estimated to result in a patient screen failure rate of approximately 80 percent. They also contribute to the extremely high costs of AD clinical trials. Developing a simpler blood-based test for assessing amyloid status would help to simplify clinical trials, reduce patient burden and reduce costs required to identify and characterize AD, particularly as clinical research begins investigating earlier stages of the disease in which patients need to be identified pre-symptomatically.

The goal of this project is to perform an independent validation of the top-performing blood plasma Aβ assays and to determine which have the highest degree of correlation with amyloid PET or CSF Aβ levels. If successful, this project will provide guidance to the research community on which assays might help to streamline clinical trials and facilitate easier and more affordable AD diagnosis.

Partners

Public Partners

  • National Institute on Aging (NIA)
  • National Institute on Mental Health (NIMH)

Private-Sector Partners

  • AbbVie Inc.*
  • Alzheimer's Association®*
  • Diagnostics Accelerator at Alzheimer's Drug Discovery Foundation*
  • Biogen MA Inc.*
  • Janssen Research & Development, LLC*
  • Takeda Pharmaceutical Company*

Academic Partners

  • Washington University School of Medicine in St. Louis
  • University of Gothenburg

*Provides financial or in-kind support for this program.

Read What the Partners are Saying

FNIH Contact

  • Wesley Horton, M.S., Scientific Project Manager, Neuroscience, whorton@fnih.org

Goals

  • Evaluate and compare top performing Aβ assays on standard validation/qualification criteria and determine each platform’s ability to differentiate between Aβ positive and negative subjects as determined by amyloid PET or CSF.  
  • Briefly determine acceptable pre-analytical processing requirements to optimize plasma Aβ bioanalysis. 
  • Determine the cutpoints in plasma Aβ peptides that offer the greatest specificity and sensitivity for predicting amyloid positivity as determined by PET imaging.  

Media

FNIH Announcement (July 26, 2021): FNIH Biomarkers Consortium Confirms Blood Tests Provide a Key Research Tool for Measuring Amyloid Accumulation in Alzheimer’s Disease

FNIH Announcement (March 12, 2020): FNIH Biomarkers Consortium Launches a Project to Select Blood Tests that Detect Early Alzheimer's Disease