@article{aaf1e535b7d24352b0c955891782001e,
title = "Predicting continuous amyloid PET values with CSF and plasma Aβ42/Aβ40",
abstract = "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.",
keywords = "CSF Aβ42/Aβ40, PET, biomarker concordance, machine learning, plasma Aβ42/Aβ40",
author = "Wisch, {Julie K.} and Gordon, {Brian A.} and Boerwinkle, {Anna H.} and Luckett, {Patrick H.} and Bollinger, {James G.} and Vitaliy Ovod and Yan Li and Henson, {Rachel L.} and Tim West and Meyer, {Mathew R.} and Kirmess, {Kristopher M.} and Benzinger, {Tammie L.S.} and Fagan, {Anne M.} and Morris, {John C.} and Bateman, {Randall J.} and Ances, {Beau M.} and Schindler, {Suzanne E.}",
note = "Funding Information: We would like to express our gratitude to the research volunteers who participate in AD clinical trials and their supportive families. This work was funded by the National Institutes of Health (NIH) grants R01AG070941 (S.E.S.), R01NR012907 (B.A.), R01NR012657 (B.A.), R01NR014449 (B.A.), K01 AG053474 (B.G.), P30 AG066444 (J.C.M.), P01AG003991 (J.C.M.), P01AG026276 (J.C.M.), U19 AG032438 (J.C.M.), and U19 AG024904 (J.C.M.). This work was also supported by the generous support of the Barnes‐Jewish Hospital Foundation; the Washington University Institute of Clinical and Translational Sciences Foundation (UL1 TR000448); the Hope Center for Neurological Disorders; the Paula and Rodger O. Riney Fund; the Daniel J Brennan MD Fund; and Fred Simmons Olga Mohan Fund and the Chan Zuckerberg Initiative (C.Z.I.). C2N Diagnostics provided measurements of plasma amyloid to Washington University at no cost. This work was supported by access to equipment made possible by the Hope Center for Neurological Disorders, the Neurogenomics and Informatics Center (NGI: https://neurogenomics.wustl.edu/ ), and the Departments of Neurology and Psychiatry at Washington University School of Medicine. Funding Information: 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 . Funding Information: We would like to express our gratitude to the research volunteers who participate in AD clinical trials and their supportive families. This work was funded by the National Institutes of Health (NIH) grants R01AG070941 (S.E.S.), R01NR012907 (B.A.), R01NR012657 (B.A.), R01NR014449 (B.A.), K01 AG053474 (B.G.), P30 AG066444 (J.C.M.), P01AG003991 (J.C.M.), P01AG026276 (J.C.M.), U19 AG032438 (J.C.M.), and U19 AG024904 (J.C.M.). This work was also supported by the generous support of the Barnes-Jewish Hospital Foundation; the Washington University Institute of Clinical and Translational Sciences Foundation (UL1 TR000448); the Hope Center for Neurological Disorders; the Paula and Rodger O. Riney Fund; the Daniel J Brennan MD Fund; and Fred Simmons Olga Mohan Fund and the Chan Zuckerberg Initiative (C.Z.I.). C2N Diagnostics provided measurements of plasma amyloid to Washington University at no cost. This work was supported by access to equipment made possible by the Hope Center for Neurological Disorders, the Neurogenomics and Informatics Center (NGI: https://neurogenomics.wustl.edu/), and the Departments of Neurology and Psychiatry at Washington University School of Medicine. Publisher Copyright: {\textcopyright} 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.",
year = "2023",
month = jan,
day = "1",
doi = "10.1002/dad2.12405",
language = "English",
volume = "15",
journal = "Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring",
issn = "2352-8729",
number = "1",
}