Plasma Aβ42/Aβ40 and phospho-tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer's disease.

Autor: Rissman RA; Department of Neurosciences, University of California San Diego, La Jolla, California, USA.; Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA.; VA San Diego Healthcare System, San Diego, California, USA., Langford O; Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA., Raman R; Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA., Donohue MC; Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA., Abdel-Latif S; Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA., Meyer MR; C2N Diagnostics, St. Louis, Missouri, USA., Wente-Roth T; C2N Diagnostics, St. Louis, Missouri, USA., Kirmess KM; C2N Diagnostics, St. Louis, Missouri, USA., Ngolab J; Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA., Winston CN; Department of Neurosciences, University of California San Diego, La Jolla, California, USA.; Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA., Jimenez-Maggiora G; Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA., Rafii MS; Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA., Sachdev P; Eisai US, Nutley, New Jersey, USA., West T; C2N Diagnostics, St. Louis, Missouri, USA., Yarasheski KE; C2N Diagnostics, St. Louis, Missouri, USA., Braunstein JB; C2N Diagnostics, St. Louis, Missouri, USA., Irizarry M; Eisai US, Nutley, New Jersey, USA., Johnson KA; Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Aisen PS; Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA., Sperling RA; Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2024 Feb; Vol. 20 (2), pp. 1214-1224. Date of Electronic Publication: 2023 Nov 06.
DOI: 10.1002/alz.13542
Abstrakt: Introduction: Incorporating blood-based Alzheimer's disease biomarkers such as tau and amyloid beta (Aβ) into screening algorithms may improve screening efficiency.
Methods: Plasma Aβ, phosphorylated tau (p-tau)181, and p-tau217 concentration levels from AHEAD 3-45 study participants were measured using mass spectrometry. Tau concentration ratios for each proteoform were calculated to normalize for inter-individual differences. Receiver operating characteristic (ROC) curve analysis was performed for each biomarker against amyloid positivity, defined by > 20 Centiloids. Mixture of experts analysis assessed the value of including tau concentration ratios into the existing predictive algorithm for amyloid positron emission tomography status.
Results: The area under the receiver operating curve (AUC) was 0.87 for Aβ42/Aβ40, 0.74 for phosphorylated variant p-tau181 ratio (p-tau181/np-tau181), and 0.92 for phosphorylated variant p-tau217 ratio (p-tau217/np-tau217). The Plasma Predicted Centiloid (PPC), a predictive model including p-tau217/np-tau217, Aβ42/Aβ40, age, and apolipoprotein E improved AUC to 0.95.
Discussion: Including plasma p-tau217/np-tau217 along with Aβ42/Aβ40 in predictive algorithms may streamline screening preclinical individuals into anti-amyloid clinical trials.
Clinicaltrials: gov Identifier: NCT04468659 HIGHLIGHTS: The addition of plasma phosphorylated variant p-tau217 ratio (p-tau217/np-tau217) significantly improved plasma biomarker algorithms for identifying preclinical amyloid positron emission tomography positivity. Prediction performance at higher NAV Centiloid levels was improved with p-tau217/np-tau217. All models generated for this study are incorporated into the Plasma Predicted Centiloid (PPC) app for public use.
(© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE
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