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 and tau status are assessed by positron emission tomography (PET) imaging or by cerebral spinal fluid (CSF) 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 simpler blood-based tests for assessing amyloid and tau 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 and pTau 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.
- Evaluate and compare top performing Aβ and phosphorylated tau (pTau) 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 and pTau bioanalysis.
- Determine the cutpoints in plasma Aβ and pTau peptides that offer the greatest specificity and sensitivity for predicting amyloid positivity as determined by PET imaging.
- Assess the sensitivity of plasma Aβ and pTau peptides for predicting disease status conversion.
- AbbVie Inc.*
- Alzheimer’s Association®*
- Diagnostics Accelerator at Alzheimer’s Drug Discovery Foundation*
- Biogen MA Inc.*
- Janssen Research & Development, LLC*
- Takeda Pharmaceutical Company*
- Indiana University School of Medicine
- University of Gothenburg
- University of Pennsylvania, Perelman School of Medicine
- Washington University School of Medicine in St. Louis
*Provides financial or in-kind support for this program.
Poster presented at Alzheimer’s Association International Conference; July 2023
Analytical Feasibility of Plasma Phospho-Tau and Aβ for Predicting Amyloid PET Positivity. Bannon, A.W.; Potter, W.Z.; Zicha, S.; Shaw, L.M.; Zetterberg, H.; Saad, Z.S.; Dage J.; Dobler I.; Raunig, D.L.; Ferber, K.; Rubel, C.E.; Schindler, S.E.; Baratta, M.; Meyers, E.A.; Rosenbaugh, E.G. Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium Plasma Abeta Project Team. Abstract published in The Journal of Prevention of Alzheimer’s Disease, December 2022.
Poster presented at Clinical Trials on Alzheimer’s Disease conference; December 2022
Zicha S., Bateman R.J., Shaw L.M., et al. Alzheimer’s Disease Neuroimaging Initiative (ADNI), Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium Plasma Aβ Project Team. Comparative analytical performance of multiple plasma Aβ42 and Aβ40 assays and their ability to predict positron emission tomography amyloid positivity. Alzheimer’s Dement. 2022
Comparative analytical performance of multiple plasma amyloid-beta assays and their relationship to amyloid PET. Zicha S., Bateman R.J., Shaw L.M., Bannon A.W., Zetterberg H, et al. Alzheimer’s Disease Neuroimaging Initiative (ADNI), Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium Plasma Aβ Project Team. Abstract published in Alzheimer’s Dement, December 2021.
Poster presented at Alzheimer’s Association International Conference; July 2021
Project data are publicly available on the ADNI Laboratory of Neuroimaging (LONI) website.
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