1. Evaluation of Blood-Based Plasma Biomarkers as Potential Markers of Amyloid Burden in Preclinical Alzheimer’s Disease
- Author
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Winston, Charisse N, Langford, Oliver, Levin, Natalie, Raman, Rema, Yarasheski, Kevin, West, Tim, Abdel-Latif, Sara, Donohue, Michael, Nakamura, Akinori, Toba, Kenji, Masters, Colin L, Doecke, James, Sperling, Reisa A, Aisen, Paul S, and Rissman, Robert A
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Dementia ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Neurosciences ,Aging ,Clinical Research ,Acquired Cognitive Impairment ,Biomedical Imaging ,Neurodegenerative ,Alzheimer's Disease ,Clinical Trials and Supportive Activities ,Prevention ,Brain Disorders ,4.1 Discovery and preclinical testing of markers and technologies ,4.2 Evaluation of markers and technologies ,Neurological ,Humans ,Alzheimer Disease ,Amyloid beta-Peptides ,Cross-Sectional Studies ,Amyloid ,Amyloidogenic Proteins ,Biomarkers ,Positron-Emission Tomography ,Peptide Fragments ,A4 ,Alzheimer's disease ,amyloid-beta ,biomarkers ,clinical trial ,mass spectrometry ,PET ,Alzheimer’s disease ,amyloid-β ,Cognitive Sciences ,Neurology & Neurosurgery ,Clinical sciences ,Biological psychology - Abstract
BackgroundParticipant eligibility for the A4 Study was determined by amyloid PET imaging. Given the disadvantages of amyloid PET imaging in accessibility and cost, blood-based biomarkers may serve as a sufficient biomarker and more cost-effective screening tool for patient enrollment into preclinical AD trials.ObjectiveTo determine if a blood-based screening test can adequately identify amyloid burden in participants screened into a preclinical AD trial.MethodsIn this cross-sectional study, 224 participants from the A4 Study received an amyloid PET scan (18Florbetapir) within 90 days of blood sample collection. Blood samples from all study participants were processed within 2 h after phlebotomy. Plasma amyloid measures were quantified by Shimazdu and C2 N Diagnostics using mass spectrometry-based platforms. A corresponding subset of blood samples (n = 100) was processed within 24 h after phlebotomy and analyzed by C2 N.ResultsPlasma Aβ42/Aβ40 demonstrated the highest association for Aβ accumulation in the brain with an AUC 0.76 (95%CI = 0.69, 0.82) at C2 N and 0.80 (95%CI = 0.75, 0.86) at Shimadzu. Blood samples processed to plasma within 2 h after phlebotomy provided a better prediction of amyloid PET status than blood samples processed within 24 h (AUC 0.80 versus 0.64; p
- Published
- 2023