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Article type: Research Article
Authors: Winston, Charisse N.a | Langford, Oliverb | Levin, Nataliea | Raman, Remab | Yarasheski, Kevinc | West, Timc | Abdel-Latif, Sarab | Donohue, Michaelb | Nakamura, Akinorid | Toba, Kenjie; f | Masters, Colin L.g | Doecke, Jamesh | Sperling, Reisa A.i | Aisen, Paul S.b | Rissman, Robert A.a; j; *
Affiliations: [a] Department of Neurosciences, University of California San Diego, La Jolla, CA, USA | [b] Alzheimer’s Therapeutic Research Institute, Keck School of Medicine University of Southern California, San Diego, CA, USA | [c] C2N Diagnostics, St. Louis, MO, USA | [d] Department of Biomarker Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan | [e] National Center for Geriatrics and Gerontology, Obu, Aichi, Japan | [f] Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan | [g] The Florey Institute, The University of Melbourne, Parkville, VIC, Australia | [h] The Commonwealth Scientific and Industrial Research Organization, Brisbane, QLD, Australia | [i] Harvard Medical School, Boston, MA, USA | [j] Department of Neurosciences, University of California San Diego and VA San Diego Healthcare System, La Jolla, CA, USA
Correspondence: [*] Correspondence to: Robert A. Rissman, Ph.D., Department of Physiology and Neuroscience, Alzheimer’s Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, 92121, Tel: 858-246-0140; Fax: 858-246-0139; E-mail: [email protected].
Abstract: Background:Participant 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. Objective:To determine if a blood-based screening test can adequately identify amyloid burden in participants screened into a preclinical AD trial. Methods:In 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. Results:Plasma 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 < 0.001). Age, sex, and APOE ɛ4 carrier status did not the diagnostic performance of plasma Aβ42/Aβ40 to predict amyloid PET positivity in A4 Study participants. Conclusion:Plasma Aβ42/Aβ40 may serve as a potential biomarker for predicting elevated amyloid in the brain. Utilizing blood testing over PET imaging may improve screening efficiency into clinical trials.
Keywords: A4, Alzheimer’s disease, amyloid-β, biomarkers, clinical trial, mass spectrometry, PET
DOI: 10.3233/JAD-221118
Journal: Journal of Alzheimer's Disease, vol. 92, no. 1, pp. 95-107, 2023
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