Patrick H Luckett1, Charlie Chen1, Brian A Gordon1, Julie Wisch1, Sarah B Berman2, Jasmeer P Chhatwal3, Carlos Cruchaga1, Anne M Fagan1, Martin R Farlow4, Nick C Fox5, Mathias Jucker6,7, Johannes Levin8,9,10, Colin L Masters11, Hiroshi Mori12, James M Noble13, Stephen Salloway14, Peter R Schofield15,16, Adam M Brickman17,18, William S Brooks15,16, David M Cash5, Michael J Fulham17,18, Bernardino Ghetti4, Clifford R Jack19, Jonathan Vöglein8,20, William E Klunk2, Robert Koeppe21, Yi Su22, Michael Weiner23,24, Qing Wang1, Daniel Marcus1, Deborah Koudelis1, Nelly Joseph-Mathurin1, Lisa Cash1, Russ Hornbeck1, Chengjie Xiong1, Richard J Perrin1, Celeste M Karch1, Jason Hassenstab1, Eric McDade1, John C Morris1, Tammie L S Benzinger1, Randall J Bateman1, Beau M Ances1. 1. Washington University in St. Louis, St. Louis, Missouri, USA. 2. University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 3. Brigham and Women's Hospital, Massachusetts General Hospital, Boston, Massachusetts, USA. 4. Indiana University, Bloomington, Indiana, USA. 5. Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK. 6. German Center for Neurodegenerative Disease, Tübingen, Germany. 7. Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. 8. Department of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany. 9. German Center for Neurodegenerative Diseases, Munich, Germany. 10. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. 11. Florey Institute, The University of Melbourne, Parkville, Victoria, Australia. 12. Osaka City University Medical School, Nagaoka Sutoku University, Abenoku, Osaka, Japan. 13. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, G.H. Sergievsky Center, and Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA. 14. Butler Hospital and Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. 15. Neuroscience Research Australia, Randwick, New South Wales, Australia. 16. School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia. 17. Department of Molecular Imaging, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. 18. The University of Sydney, Sydney, New South Wales, Australia. 19. Mayo Clinic, Rochester, Minnesota, USA. 20. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany. 21. University of Michigan, Michigan, Ann Arbor, USA. 22. Banner Alzheimer Institute, Phoenix, Arizona, USA. 23. University of California San Francisco, San Francisco, California, USA. 24. San Francisco Veterans Affairs Medical Center, San Francisco, California, USA.
Abstract
INTRODUCTION: As the number of biomarkers used to study Alzheimer's disease (AD) continues to increase, it is important to understand the utility of any given biomarker, as well as what additional information a biomarker provides when compared to others. METHODS: We used hierarchical clustering to group 19 cross-sectional biomarkers in autosomal dominant AD. Feature selection identified biomarkers that were the strongest predictors of mutation status and estimated years from symptom onset (EYO). Biomarkers identified included clinical assessments, neuroimaging, cerebrospinal fluid amyloid, and tau, and emerging biomarkers of neuronal integrity and inflammation. RESULTS: Three primary clusters were identified: neurodegeneration, amyloid/tau, and emerging biomarkers. Feature selection identified amyloid and tau measures as the primary predictors of mutation status and EYO. Emerging biomarkers of neuronal integrity and inflammation were relatively weak predictors. DISCUSSION: These results provide novel insight into our understanding of the relationships among biomarkers and the staging of biomarkers based on disease progression.
INTRODUCTION: As the number of biomarkers used to study Alzheimer's disease (AD) continues to increase, it is important to understand the utility of any given biomarker, as well as what additional information a biomarker provides when compared to others. METHODS: We used hierarchical clustering to group 19 cross-sectional biomarkers in autosomal dominant AD. Feature selection identified biomarkers that were the strongest predictors of mutation status and estimated years from symptom onset (EYO). Biomarkers identified included clinical assessments, neuroimaging, cerebrospinal fluid amyloid, and tau, and emerging biomarkers of neuronal integrity and inflammation. RESULTS: Three primary clusters were identified: neurodegeneration, amyloid/tau, and emerging biomarkers. Feature selection identified amyloid and tau measures as the primary predictors of mutation status and EYO. Emerging biomarkers of neuronal integrity and inflammation were relatively weak predictors. DISCUSSION: These results provide novel insight into our understanding of the relationships among biomarkers and the staging of biomarkers based on disease progression.
Authors: Rebecca Craig-Schapiro; Richard J Perrin; Catherine M Roe; Chengjie Xiong; Deborah Carter; Nigel J Cairns; Mark A Mintun; Elaine R Peskind; Ge Li; Douglas R Galasko; Christopher M Clark; Joseph F Quinn; Gina D'Angelo; James P Malone; R Reid Townsend; John C Morris; Anne M Fagan; David M Holtzman Journal: Biol Psychiatry Date: 2010-11-15 Impact factor: 13.382
Authors: Eric McDade; Guoqiao Wang; Brian A Gordon; Jason Hassenstab; Tammie L S Benzinger; Virginia Buckles; Anne M Fagan; David M Holtzman; Nigel J Cairns; Alison M Goate; Daniel S Marcus; John C Morris; Katrina Paumier; Chengjie Xiong; Ricardo Allegri; Sarah B Berman; William Klunk; James Noble; John Ringman; Bernardino Ghetti; Martin Farlow; Reisa A Sperling; Jasmeer Chhatwal; Stephen Salloway; Neill R Graff-Radford; Peter R Schofield; Colin Masters; Martin N Rossor; Nick C Fox; Johannes Levin; Mathias Jucker; Randall J Bateman Journal: Neurology Date: 2018-09-14 Impact factor: 9.910
Authors: Davis C Ryman; Natalia Acosta-Baena; Paul S Aisen; Thomas Bird; Adrian Danek; Nick C Fox; Alison Goate; Peter Frommelt; Bernardino Ghetti; Jessica B S Langbaum; Francisco Lopera; Ralph Martins; Colin L Masters; Richard P Mayeux; Eric McDade; Sonia Moreno; Eric M Reiman; John M Ringman; Steve Salloway; Peter R Schofield; Reisa Sperling; Pierre N Tariot; Chengjie Xiong; John C Morris; Randall J Bateman Journal: Neurology Date: 2014-06-13 Impact factor: 9.910
Authors: Anne M Fagan; Chengjie Xiong; Mateusz S Jasielec; Randall J Bateman; Alison M Goate; Tammie L S Benzinger; Bernardino Ghetti; Ralph N Martins; Colin L Masters; Richard Mayeux; John M Ringman; Martin N Rossor; Stephen Salloway; Peter R Schofield; Reisa A Sperling; Daniel Marcus; Nigel J Cairns; Virginia D Buckles; Jack H Ladenson; John C Morris; David M Holtzman Journal: Sci Transl Med Date: 2014-03-05 Impact factor: 17.956
Authors: Randall J Bateman; Paul S Aisen; Bart De Strooper; Nick C Fox; Cynthia A Lemere; John M Ringman; Stephen Salloway; Reisa A Sperling; Manfred Windisch; Chengjie Xiong Journal: Alzheimers Res Ther Date: 2011-01-06 Impact factor: 6.982
Authors: Patrick H Luckett; Austin McCullough; Brian A Gordon; Jeremy Strain; Shaney Flores; Aylin Dincer; John McCarthy; Todd Kuffner; Ari Stern; Karin L Meeker; Sarah B Berman; Jasmeer P Chhatwal; Carlos Cruchaga; Anne M Fagan; Martin R Farlow; Nick C Fox; Mathias Jucker; Johannes Levin; Colin L Masters; Hiroshi Mori; James M Noble; Stephen Salloway; Peter R Schofield; Adam M Brickman; William S Brooks; David M Cash; Michael J Fulham; Bernardino Ghetti; Clifford R Jack; Jonathan Vöglein; William Klunk; Robert Koeppe; Hwamee Oh; Yi Su; Michael Weiner; Qing Wang; Laura Swisher; Dan Marcus; Deborah Koudelis; Nelly Joseph-Mathurin; Lisa Cash; Russ Hornbeck; Chengjie Xiong; Richard J Perrin; Celeste M Karch; Jason Hassenstab; Eric McDade; John C Morris; Tammie L S Benzinger; Randall J Bateman; Beau M Ances Journal: Alzheimers Dement Date: 2021-01-21 Impact factor: 16.655
Authors: Lirong Yan; Collin Y Liu; Koon-Pong Wong; Sung-Cheng Huang; Wendy J Mack; Kay Jann; Giovanni Coppola; John M Ringman; Danny J J Wang Journal: Neuroimage Clin Date: 2017-12-06 Impact factor: 4.891
Authors: Val J Lowe; Emily Lundt; David Knopman; Matthew L Senjem; Jeffrey L Gunter; Christopher G Schwarz; Bradley J Kemp; Clifford R Jack; Ronald C Petersen Journal: Neuroimage Clin Date: 2017-08-14 Impact factor: 4.881