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

A recently proposed new research framework defines patients affected by Alzheimer’s Disease (AD) based on pathological hallmarks, instead of symptoms or signs such as mild cognitive impairment (MCI). This research framework is intended to help guide studies developing potential new treatments for AD. The core of the research framework is to define patients according to the following biomarker levels: amyloid (Aβ), tau, and neurodegeneration status (A/T/N).

Currently, amyloid status can be assessed by imaging amyloid PET or Cerebral Spinal Fluid (CSF) Aβ measurements, both of which are either extremely costly (PET) or require invasive procedures (CSF lumbar puncture). Both of these procedures, and the aspiration to define patients by these criteria, are estimated to result in ~80% patient screen failure rate and contribute to the extremely high costs of clinical trials in Alzheimer’s Disease. Ideally, a much simpler blood-based test for amyloid status would help to simplify clinical trials, reduce patient burden, and reduce the costs required to identify and characterize AD, particularly as clinical research moves into earlier stages of the disease where patients need to be identified in a pre-symptomatic state (no cognitive impairments).

The goal of this project is to perform an independent validation of the top performing blood plasma Aβ assays and determine which are the most robust in terms of having a high degree of correlation with amyloid PET or CSF Aβ levels. The desired outcome is to offer the research community guidance on which assays might help streamline clinical trials and aid in AD diagnosis.

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.  

Results & Accomplishments

Media

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

Partners

Public Partners:
National Institute on Aging (NIA)
National Institute on Mental Health (NIMH)

Private 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.
 

FNIH Contact

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