Predicting continuous amyloid PET values with CSF and plasma Aβ42/Aβ40.

Autor: Wisch JK; Department of Neurology Washington University in Saint Louis St. Louis Missouri USA., Gordon BA; Department of Radiology Washington University in Saint Louis St. Louis Missouri USA.; Hope Center Washington University in Saint Louis St. Louis Missouri USA.; Knight Alzheimer Disease Research Center Washington University School of Medicine St Louis Missouri USA., Boerwinkle AH; Department of Neurology Washington University in Saint Louis St. Louis Missouri USA., Luckett PH; Department of Neurology Washington University in Saint Louis St. Louis Missouri USA., Bollinger JG; Department of Neurology Washington University in Saint Louis St. Louis Missouri USA.; The Tracy Family SILQ Center for Neurodegenerative Biology St. Louis Missouri USA., Ovod V; Department of Neurology Washington University in Saint Louis St. Louis Missouri USA.; The Tracy Family SILQ Center for Neurodegenerative Biology St. Louis Missouri USA., Li Y; Department of Radiology Washington University in Saint Louis St. Louis Missouri USA., Henson RL; Department of Neurology Washington University in Saint Louis St. Louis Missouri USA., West T; C2N Diagnostics St. Louis Missouri USA., Meyer MR; C2N Diagnostics St. Louis Missouri USA., Kirmess KM; C2N Diagnostics St. Louis Missouri USA., Benzinger TLS; Department of Radiology Washington University in Saint Louis St. Louis Missouri USA.; Knight Alzheimer Disease Research Center Washington University School of Medicine St Louis Missouri USA., Fagan AM; Department of Neurology Washington University in Saint Louis St. Louis Missouri USA.; Knight Alzheimer Disease Research Center Washington University School of Medicine St Louis Missouri USA., Morris JC; Department of Neurology Washington University in Saint Louis St. Louis Missouri USA.; Knight Alzheimer Disease Research Center Washington University School of Medicine St Louis Missouri USA., Bateman RJ; Department of Neurology Washington University in Saint Louis St. Louis Missouri USA.; The Tracy Family SILQ Center for Neurodegenerative Biology St. Louis Missouri USA., Ances BM; Department of Neurology Washington University in Saint Louis St. Louis Missouri USA.; Department of Radiology Washington University in Saint Louis St. Louis Missouri USA.; Hope Center Washington University in Saint Louis St. Louis Missouri USA.; Knight Alzheimer Disease Research Center Washington University School of Medicine St Louis Missouri USA., Schindler SE; Department of Neurology Washington University in Saint Louis St. Louis Missouri USA.; Knight Alzheimer Disease Research Center Washington University School of Medicine St Louis Missouri USA.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia (Amsterdam, Netherlands) [Alzheimers Dement (Amst)] 2023 Mar 02; Vol. 15 (1), pp. e12405. Date of Electronic Publication: 2023 Mar 02 (Print Publication: 2023).
DOI: 10.1002/dad2.12405
Abstrakt: Introduction: Continuous measures of amyloid burden as measured by positron emission tomography (PET) are being used increasingly to stage Alzheimer's disease (AD). This study examined whether cerebrospinal fluid (CSF) and plasma amyloid beta (Aβ)42/Aβ40 could predict continuous values for amyloid PET.
Methods: CSF Aβ42 and Aβ40 were measured with automated immunoassays. Plasma Aβ42 and Aβ40 were measured with an immunoprecipitation-mass spectrometry assay. Amyloid PET was performed with Pittsburgh compound B (PiB). The continuous relationships of CSF and plasma Aβ42/Aβ40 with amyloid PET burden were modeled.
Results: Most participants were cognitively normal (427 of 491 [87%]) and the mean age was 69.0 ± 8.8 years. CSF Aβ42/Aβ40 predicted amyloid PET burden until a relatively high level of amyloid accumulation (69.8 Centiloids), whereas plasma Aβ42/Aβ40 predicted amyloid PET burden until a lower level (33.4 Centiloids).
Discussion: CSF Aβ42/Aβ40 predicts the continuous level of amyloid plaque burden over a wider range than plasma Aβ42/Aβ40 and may be useful in AD staging.
Highlights: Cerebrospinal fluid (CSF) amyloid beta (Aβ)42/Aβ40 predicts continuous amyloid positron emission tomography (PET) values up to a relatively high burden.Plasma Aβ42/Aβ40 is a comparatively dichotomous measure of brain amyloidosis.Models can predict regional amyloid PET burden based on CSF Aβ42/Aβ40.CSF Aβ42/Aβ40 may be useful in staging AD.
Competing Interests: Julie K. Wisch, Anna H. Boerwinkle, Patrick H. Luckett, Yan Li, Rachel L. Henson, and Beau M. Ances report no disclosures. Brian A. Gordon receives research support from Eli Lilly and Avid Radiopharmaceuticals. James G. Bollinger and Vitaliy Ovod have submitted the US provisional patent application “Plasma Based Methods for Detecting CNS Amyloid Deposition” as co‐inventors and may receive royalty income based on technology (stable isotope labeling kinetics and blood plasma assay) licensed by Washington University to C2N Diagnostics. Tim West, Mathew R. Meyer, and Kristopher M. Kirmess are employees of C2N Diagnostics, which offers the plasma Aβ42/Aβ40 assay used in this article. Tammie L.S. Benzinger has consulted on clinical trials with Biogen, Roche, Janssen, and Eli Lilly. She receives research support from Eli Lilly and Avid Radiopharmaceuticals. Neither John C. Morris nor his family owns stock or has equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company. Randall J. Bateman co‐founded C2N Diagnostics, which offers the PrecivityAD blood test. Washington University and Randall J. Bateman have equity ownership interest in C2N Diagnostics and receive royalty income based on technology (stable isotope labeling kinetics and blood plasma assay) licensed by Washington University to C2N Diagnostics. Randall J. Bateman has received research funding from Avid Radiopharmaceuticals, Janssen, Roche/Genentech, Eli Lilly, Eisai, Biogen, AbbVie, Bristol Myers Squibb, and Novartis. Randall J. Bateman serves on the Roche Gantenerumab Steering Committee as an unpaid member. Suzanne E. Schindler has analyzed data provided by C2N Diagnostics to Washington University at no cost. She has not received any research funding or personal compensation from C2N Diagnostics or any other for‐profit organization. Author disclosures are available in the supporting information.
(© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE
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