Thomas J Montine1, Sarah E Monsell2, Thomas G Beach3, Eileen H Bigio4, Yunqi Bu2, Nigel J Cairns5, Matthew Frosch6, Jonathan Henriksen7, Julia Kofler8, Walter A Kukull2, Edward B Lee9, Peter T Nelson10, Aimee M Schantz7, Julie A Schneider11, Joshua A Sonnen7, John Q Trojanowski9, Harry V Vinters12, Xiao-Hua Zhou2, Bradley T Hyman13. 1. Department of Pathology, University of Washington, Seattle, WA, USA. Electronic address: tmontine@u.washington.edu. 2. National Alzheimer Coordinating Center, University of Washington, Seattle, WA, USA. 3. Banner Sun Health Research Institute, Civin Laboratory for Neuropathology, Sun City, AZ, USA. 4. Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 5. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. 6. Department of Pathology, C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Charleston, MA, USA. 7. Department of Pathology, University of Washington, Seattle, WA, USA. 8. Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA. 9. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. 10. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Pathology Department, University of Kentucky, Lexington, KY, USA. 11. Department of Pathology Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA. 12. Department of Pathology & Laboratory Medicine (Neuropathology) David Geffen School of Medicine at UCLA, and Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine at UCLA, and Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA. 13. Department of Neurology, Massachusetts General Hospital, Charleston, MA, USA; Massachusetts Alzheimer's Disease Research Center, Massachusetts General Hospital, Charleston, MA, USA.
Abstract
INTRODUCTION: Neuropathologic assessment is the current "gold standard" for evaluating the Alzheimer's disease (AD), but there is no consensus on the methods used. METHODS: Fifteen unstained slides (8 brain regions) from each of the 14 cases were prepared and distributed to 10 different National Institute on Aging AD Centers for application of usual staining and evaluation following recently revised guidelines for AD neuropathologic change. RESULTS: Current practice used in the AD Centers Program achieved robustly excellent agreement for the severity score for AD neuropathologic change (average weighted κ = .88, 95% confidence interval: 0.77-0.95) and good-to-excellent agreement for the three supporting scores. Some improvement was observed with consensus evaluation but not with central staining of slides. Evaluation of glass slides and digitally prepared whole-slide images was comparable. DISCUSSION: AD neuropathologic evaluation as performed across AD Centers yields data that have high agreement with potential modifications for modest improvements.
INTRODUCTION: Neuropathologic assessment is the current "gold standard" for evaluating the Alzheimer's disease (AD), but there is no consensus on the methods used. METHODS: Fifteen unstained slides (8 brain regions) from each of the 14 cases were prepared and distributed to 10 different National Institute on Aging AD Centers for application of usual staining and evaluation following recently revised guidelines for AD neuropathologic change. RESULTS: Current practice used in the AD Centers Program achieved robustly excellent agreement for the severity score for AD neuropathologic change (average weighted κ = .88, 95% confidence interval: 0.77-0.95) and good-to-excellent agreement for the three supporting scores. Some improvement was observed with consensus evaluation but not with central staining of slides. Evaluation of glass slides and digitally prepared whole-slide images was comparable. DISCUSSION: AD neuropathologic evaluation as performed across AD Centers yields data that have high agreement with potential modifications for modest improvements.
Authors: Thomas J Montine; Creighton H Phelps; Thomas G Beach; Eileen H Bigio; Nigel J Cairns; Dennis W Dickson; Charles Duyckaerts; Matthew P Frosch; Eliezer Masliah; Suzanne S Mirra; Peter T Nelson; Julie A Schneider; Dietmar Rudolf Thal; John Q Trojanowski; Harry V Vinters; Bradley T Hyman Journal: Acta Neuropathol Date: 2011-11-20 Impact factor: 17.088
Authors: Bradley T Hyman; Creighton H Phelps; Thomas G Beach; Eileen H Bigio; Nigel J Cairns; Maria C Carrillo; Dennis W Dickson; Charles Duyckaerts; Matthew P Frosch; Eliezer Masliah; Suzanne S Mirra; Peter T Nelson; Julie A Schneider; Dietmar Rudolf Thal; Bill Thies; John Q Trojanowski; Harry V Vinters; Thomas J Montine Journal: Alzheimers Dement Date: 2012-01 Impact factor: 21.566
Authors: S S Mirra; A Heyman; D McKeel; S M Sumi; B J Crain; L M Brownlee; F S Vogel; J P Hughes; G van Belle; L Berg Journal: Neurology Date: 1991-04 Impact factor: 9.910
Authors: Irina Alafuzoff; Maria Pikkarainen; Thomas Arzberger; Dietmar R Thal; Safa Al-Sarraj; Jeanne Bell; Istvan Bodi; Herbert Budka; Estibaliz Capetillo-Zarate; Isidro Ferrer; Ellen Gelpi; Stephen Gentleman; Giorgio Giaccone; Nikolaos Kavantzas; Andrew King; Penelope Korkolopoulou; Gábor G Kovács; David Meyronet; Camelia Monoranu; Piero Parchi; Efstratios Patsouris; Wolfgang Roggendorf; Christine Stadelmann; Nathalie Streichenberger; Fabricio Tagliavini; Hans Kretzschmar Journal: Acta Neuropathol Date: 2008-03-15 Impact factor: 17.088
Authors: Janna Hackett Neltner; Erin Lynn Abner; Frederick A Schmitt; Stephanie Kay Denison; Sonya Anderson; Ela Patel; Peter T Nelson Journal: J Neuropathol Exp Neurol Date: 2012-12 Impact factor: 3.685
Authors: Irina Alafuzoff; Maria Pikkarainen; Safa Al-Sarraj; Thomas Arzberger; Jeanne Bell; Istvan Bodi; Nenad Bogdanovic; Herbert Budka; Orso Bugiani; Isidro Ferrer; Ellen Gelpi; Giorgio Giaccone; Manuel B Graeber; Jean-Jacques Hauw; Wouter Kamphorst; Andrew King; Nicolas Kopp; Penelope Korkolopoulou; Gábor G Kovács; David Meyronet; Piero Parchi; Efstratios Patsouris; Matthias Preusser; Rivka Ravid; Wolfgang Roggendorf; Danielle Seilhean; Nathalie Streichenberger; Dietmar R Thal; Hans Kretzschmar Journal: J Neuropathol Exp Neurol Date: 2006-08 Impact factor: 3.685
Authors: Heiko Braak; Irina Alafuzoff; Thomas Arzberger; Hans Kretzschmar; Kelly Del Tredici Journal: Acta Neuropathol Date: 2006-08-12 Impact factor: 17.088
Authors: Stefan Prokop; Kelly R Miller; Sergio R Labra; Rose M Pitkin; Kevt'her Hoxha; Sneha Narasimhan; Lakshmi Changolkar; Alyssa Rosenbloom; Virginia M-Y Lee; John Q Trojanowski Journal: Acta Neuropathol Date: 2019-07-26 Impact factor: 17.088
Authors: Margaret E Flanagan; Desiree A Marshall; Jane B Shofer; Kathleen S Montine; Peter T Nelson; Thomas J Montine; C Dirk Keene Journal: J Neuropathol Exp Neurol Date: 2017-01-01 Impact factor: 3.685
Authors: David J Irwin; Murray Grossman; Daniel Weintraub; Howard I Hurtig; John E Duda; Sharon X Xie; Edward B Lee; Vivianna M Van Deerlin; Oscar L Lopez; Julia K Kofler; Peter T Nelson; Gregory A Jicha; Randy Woltjer; Joseph F Quinn; Jeffery Kaye; James B Leverenz; Debby Tsuang; Katelan Longfellow; Dora Yearout; Walter Kukull; C Dirk Keene; Thomas J Montine; Cyrus P Zabetian; John Q Trojanowski Journal: Lancet Neurol Date: 2017-01 Impact factor: 44.182
Authors: Lilah M Besser; Walter A Kukull; Merilee A Teylan; Eileen H Bigio; Nigel J Cairns; Julia K Kofler; Thomas J Montine; Julie A Schneider; Peter T Nelson Journal: J Neuropathol Exp Neurol Date: 2018-08-01 Impact factor: 3.685
Authors: Zhuohao He; Jing L Guo; Jennifer D McBride; Sneha Narasimhan; Hyesung Kim; Lakshmi Changolkar; Bin Zhang; Ronald J Gathagan; Cuiyong Yue; Christopher Dengler; Anna Stieber; Magdalena Nitla; Douglas A Coulter; Ted Abel; Kurt R Brunden; John Q Trojanowski; Virginia M-Y Lee Journal: Nat Med Date: 2017-12-04 Impact factor: 53.440
Authors: Rajnish Bharadwaj; Patrick J Cimino; Margaret E Flanagan; Caitlin S Latimer; Luis F Gonzalez-Cuyar; Gordana Juric-Sekhar; Thomas J Montine; Desiree A Marshall; C Dirk Keene Journal: Histopathology Date: 2017-11-22 Impact factor: 5.087
Authors: Alberto Lleó; David J Irwin; Ignacio Illán-Gala; Corey T McMillan; David A Wolk; Edward B Lee; Vivianna M Van Deerlin; Leslie M Shaw; John Q Trojanowski; Murray Grossman Journal: JAMA Neurol Date: 2018-06-01 Impact factor: 18.302
Authors: Gabor G Kovacs; Isidro Ferrer; Lea T Grinberg; Irina Alafuzoff; Johannes Attems; Herbert Budka; Nigel J Cairns; John F Crary; Charles Duyckaerts; Bernardino Ghetti; Glenda M Halliday; James W Ironside; Seth Love; Ian R Mackenzie; David G Munoz; Melissa E Murray; Peter T Nelson; Hitoshi Takahashi; John Q Trojanowski; Olaf Ansorge; Thomas Arzberger; Atik Baborie; Thomas G Beach; Kevin F Bieniek; Eileen H Bigio; Istvan Bodi; Brittany N Dugger; Mel Feany; Ellen Gelpi; Stephen M Gentleman; Giorgio Giaccone; Kimmo J Hatanpaa; Richard Heale; Patrick R Hof; Monika Hofer; Tibor Hortobágyi; Kurt Jellinger; Gregory A Jicha; Paul Ince; Julia Kofler; Enikö Kövari; Jillian J Kril; David M Mann; Radoslav Matej; Ann C McKee; Catriona McLean; Ivan Milenkovic; Thomas J Montine; Shigeo Murayama; Edward B Lee; Jasmin Rahimi; Roberta D Rodriguez; Annemieke Rozemüller; Julie A Schneider; Christian Schultz; William Seeley; Danielle Seilhean; Colin Smith; Fabrizio Tagliavini; Masaki Takao; Dietmar Rudolf Thal; Jon B Toledo; Markus Tolnay; Juan C Troncoso; Harry V Vinters; Serge Weis; Stephen B Wharton; Charles L White; Thomas Wisniewski; John M Woulfe; Masahito Yamada; Dennis W Dickson Journal: Acta Neuropathol Date: 2015-12-10 Impact factor: 17.088