Catherine Pan1, Ané Korff1, Douglas Galasko2, Carmen Ginghina1, Elaine Peskind3, Ge Li4, Joseph Quinn5, Thomas J Montine1, Kevin Cain6, Min Shi1, Jing Zhang1. 1. Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA. 2. Department of Neurosciences, University of California at San Diego, San Diego, CA, USA. 3. Northwest Network VISN-20 Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA. 4. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA. 5. Department of Neurology, Oregon Health and Science University, Portland, OR, USA Portland VA Medical Center, Portland, OR, USA. 6. Department of Biostatistics, University of Washington School of Medicine, Seattle, WA, USA.
Abstract
BACKGROUND: Meso Scale Discovery (MSD) recently established electrochemiluminescence-based assays to measure cerebrospinal fluid (CSF) levels of total tau (t-tau) and amyloid-β 1-42 peptide (Aβ42) that can aid in the diagnosis of Alzheimer's disease (AD). The goal of this investigation is to independently evaluate this platform and establish cut-off values of these biomarkers for AD diagnosis. OBJECTIVE: To validate the analytical and clinical performance of the MSD t-tau and Aβ42 kits and propose diagnostic cut-off values for the field. METHODS: The analytical performance of the CSF t-tau and Aβ42 assays was determined, followed by assessment of diagnostic performance of CSF t-tau, Aβ42, and t-tau/Aβ42 in three clinically characterized cohorts. RESULTS: Both MSD assays demonstrated consistent and stable analytical performance, as well as resistance to several important pre-analytic variables. Diagnostically, t-tau/Aβ42 performed the best. CONCLUSIONS: Our results independently confirm the analytical and clinical performance of the MSD CSF t-tau and Aβ42 assays. Based on a large, multi-center, clinically-diagnosed cohort, we propose for the first time candidate diagnostic cut-offs for MSD measured CSF t-tau, Aβ42, and t-tau/Aβ42. However, these values needs to be refined as more subjects are included and the assays are tested by other laboratories.
BACKGROUND: Meso Scale Discovery (MSD) recently established electrochemiluminescence-based assays to measure cerebrospinal fluid (CSF) levels of total tau (t-tau) and amyloid-β 1-42 peptide (Aβ42) that can aid in the diagnosis of Alzheimer's disease (AD). The goal of this investigation is to independently evaluate this platform and establish cut-off values of these biomarkers for AD diagnosis. OBJECTIVE: To validate the analytical and clinical performance of the MSDt-tau and Aβ42 kits and propose diagnostic cut-off values for the field. METHODS: The analytical performance of the CSF t-tau and Aβ42 assays was determined, followed by assessment of diagnostic performance of CSF t-tau, Aβ42, and t-tau/Aβ42 in three clinically characterized cohorts. RESULTS: Both MSD assays demonstrated consistent and stable analytical performance, as well as resistance to several important pre-analytic variables. Diagnostically, t-tau/Aβ42 performed the best. CONCLUSIONS: Our results independently confirm the analytical and clinical performance of the MSD CSFt-tau and Aβ42 assays. Based on a large, multi-center, clinically-diagnosed cohort, we propose for the first time candidate diagnostic cut-offs for MSD measured CSF t-tau, Aβ42, and t-tau/Aβ42. However, these values needs to be refined as more subjects are included and the assays are tested by other laboratories.
Entities:
Keywords:
Alzheimer's disease; Aβ$^{42}$; Meso Scale Discovery; cerebrospinal fluid; tau
Authors: Binodh DeSilva; Wendell Smith; Russell Weiner; Marian Kelley; JoMarie Smolec; Ben Lee; Masood Khan; Richard Tacey; Howard Hill; Abbie Celniker Journal: Pharm Res Date: 2003-11 Impact factor: 4.200
Authors: Niklas Mattsson; Ulf Andreasson; Staffan Persson; Maria C Carrillo; Steven Collins; Sonia Chalbot; Neal Cutler; Diane Dufour-Rainfray; Anne M Fagan; Niels H H Heegaard; Ging-Yuek Robin Hsiung; Bradley Hyman; Khalid Iqbal; Stephan A Kaeser; Stephan A Käser; D Richard Lachno; Alberto Lleó; Piotr Lewczuk; José L Molinuevo; Piero Parchi; Axel Regeniter; Robert A Rissman; Robert Rissman; Hanna Rosenmann; Giuseppe Sancesario; Johannes Schröder; Leslie M Shaw; Charlotte E Teunissen; John Q Trojanowski; Hugo Vanderstichele; Manu Vandijck; Marcel M Verbeek; Henrik Zetterberg; Kaj Blennow Journal: Alzheimers Dement Date: 2013-05 Impact factor: 21.566
Authors: Yu Wang; Min Shi; Kathryn A Chung; Cyrus P Zabetian; James B Leverenz; Daniela Berg; Karin Srulijes; John Q Trojanowski; Virginia M-Y Lee; Andrew D Siderowf; Howard Hurtig; Irene Litvan; Mya C Schiess; Elaine R Peskind; Masami Masuda; Masato Hasegawa; Xiangmin Lin; Catherine Pan; Douglas Galasko; David S Goldstein; Poul Henning Jensen; Hui Yang; Kevin C Cain; Jing Zhang Journal: Sci Transl Med Date: 2012-02-15 Impact factor: 17.956
Authors: Anne M Fagan; Leslie M Shaw; Chengjie Xiong; Hugo Vanderstichele; Mark A Mintun; John Q Trojanowski; Els Coart; John C Morris; David M Holtzman Journal: Arch Neurol Date: 2011-05-09
Authors: Min Shi; Joshua Bradner; Aneeka M Hancock; Kathryn A Chung; Joseph F Quinn; Elaine R Peskind; Douglas Galasko; Joseph Jankovic; Cyrus P Zabetian; Hojoong M Kim; James B Leverenz; Thomas J Montine; Carmen Ginghina; Un Jung Kang; Kevin C Cain; Yu Wang; Jan Aasly; David Goldstein; Jing Zhang Journal: Ann Neurol Date: 2011-03-11 Impact factor: 10.422
Authors: Leslie M Shaw; Hugo Vanderstichele; Malgorzata Knapik-Czajka; Christopher M Clark; Paul S Aisen; Ronald C Petersen; Kaj Blennow; Holly Soares; Adam Simon; Piotr Lewczuk; Robert Dean; Eric Siemers; William Potter; Virginia M-Y Lee; John Q Trojanowski Journal: Ann Neurol Date: 2009-04 Impact factor: 10.422
Authors: C F Lippa; H Fujiwara; D M Mann; B Giasson; M Baba; M L Schmidt; L E Nee; B O'Connell; D A Pollen; P St George-Hyslop; B Ghetti; D Nochlin; T D Bird; N J Cairns; V M Lee; T Iwatsubo; J Q Trojanowski Journal: Am J Pathol Date: 1998-11 Impact factor: 4.307
Authors: Franc Llorens; Niels Kruse; Matthias Schmitz; Mohsin Shafiq; José Eriton Gomes da Cunha; Nadine Gotzman; Saima Zafar; Katrin Thune; João Ricardo Mendes de Oliveira; Brit Mollenhauer; Inga Zerr Journal: J Neurol Date: 2015-07-11 Impact factor: 4.849
Authors: Gwënaël Pottiez; Li Yang; Tessandra Stewart; Ning Song; Patrick Aro; Douglas R Galasko; Joseph F Quinn; Elaine R Peskind; Min Shi; Jing Zhang Journal: J Proteome Res Date: 2017-02-07 Impact factor: 4.466
Authors: Giuseppe Barisano; Axel Montagne; Kassandra Kisler; Julie A Schneider; Joanna M Wardlaw; Berislav V Zlokovic Journal: Nat Cardiovasc Res Date: 2022-02-07
Authors: Jack T Wiedrick; Jay I Phillips; Theresa A Lusardi; Trevor J McFarland; Babett Lind; Ursula S Sandau; Christina A Harrington; Jodi A Lapidus; Douglas R Galasko; Joseph F Quinn; Julie A Saugstad Journal: J Alzheimers Dis Date: 2019 Impact factor: 4.472
Authors: Xianghong Arakaki; Shao-Min Hung; Roger Rochart; Alfred N Fonteh; Michael G Harrington Journal: Neurobiol Aging Date: 2021-12-05 Impact factor: 4.673