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Update on the biomarker core of the Alzheimer's Disease Neuroimaging Initiative subjects
Authors:John Q Trojanowski  Hugo Vandeerstichele  Magdalena Korecka  Christopher M Clark  Paul S Aisen  Ronald C Petersen  Kaj Blennow  Holly Soares  Adam Simon  Piotr Lewczuk  Robert Dean  Eric Siemers  William Z Potter  Michael W Weiner  Clifford R Jack  William Jagust  Arthur W Toga  Virginia M-Y Lee  Leslie M Shaw
Institution:1. Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA;2. Department of Diagnostic Development, Innogenetics NV, Gent, Belgium;3. Department of Neurology, Institute of Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA;4. University of California San Diego, CA, USA;5. Mayo Clinic College of Medicine, Rochester, MN, USA;6. Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at Göteborg University, Mölndal, Sweden;7. Pfizer Global Research and Development, Groton, CT, USA;8. Merck Research Laboratories, West Point, PA, USA;9. Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany;10. Eli Lilly & Company, Indianapolis, IN, USA;11. VA Medical Center, San Francisco, CA, USA;12. University of California Berkeley, CA, USA;13. UCLA School of Medicine, Los Angeles, CA, USA;1. Medical and Scientific Relations, Alzheimer''s Association, Chicago, IL, USA;2. Department of Medicine, Brigham and Women''s Hospital, Inc., Boston, MA, USA;3. Biomarker and Research Division, Nordic Biosciences, Copenhagen, Denmark;4. NextGen Sciences Dx, Gainesville, FL, USA;5. Institute of Psychiatry, Department of Medicine and Neurosciences, King''s College, London, UK;6. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA;7. Internal Medicine Department, University of North Texas Health Sciences Center at Fort Worth, Fort Worth, TX, USA;8. Araclon Biotech, Zaragoza, Spain;9. Diagenic ASA, Oslo, Norway;10. Bristol Myers Squibb, Co., Wallingford, CT, USA;11. University of Southampton, Southampton, UK;12. Department of Neurology, Mayo Clinic, Rochester, MN, USA;13. Proteome Sciences plc, London, UK;14. C2N Diagnostics, St Louis, MO, USA;15. Independent Science Writer, Philadelphia, PA, USA;p. Alzheimer''s Drug Discovery Foundation, New York, NY, USA;q. School of Medicine, University of California–San Francisco, San Francisco, CA, USA;r. Department of Veterans Affairs Medical Center, San Francisco, CA, USA;1. Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain;2. Centre of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Madrid, Spain;3. Center for Research and Advanced Therapies, Fundación CITA-alzheimer Fundazioa, San Sebastian, Spain;4. Amsterdam UMC, Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands;5. Centre for Memory Disturbances, Section of Neurology, Lab of Clinical Neurochemistry, University of Perugia, Perugia, Italy;6. Centre for the Studies on the Prevention of Alzheimer''s Disease, Douglas Mental Health University Institute, Montréal, QC, Canada;7. Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;8. Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Nijmegen, the Netherlands;9. Department of Laboratory Medicine, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Nijmegen, the Netherlands;10. Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands;11. 1st Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Makedonia, Greece;12. Alzheimer Hellas, Thessaloniki, Greece;13. University Hospital Leuven, Leuven, Belgium;14. Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium;15. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet Center for Alzheimer Research, Division of Clinical Geriatrics, Huddinge and Department of Old Age Psychiatry, Psychology and Neuroscience, King''s College London, London, UK;p. Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany;q. Dementia Clinic, Centro Hospitalar e Universitário de Coimbra and Faculty of Medicine, Universidade de Coimbra, Coimbra, Portugal;r. ICN Hospital Clinic i Universitari, Barcelona, Spain;s. Univ Montpellier, CHU Montpellier, Montpellier, France;t. Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden;u. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden;v. Department of Neurodegenerative Disease, University College London, Queen Square, London, United Kingdom;w. UK Dementia Research Institute at UCL, London, United Kingdom;1. Institute of Memory and Alzheimer''s Disease (IM2A) and Brain and Spine Institute (ICM) UMR S 1127 Frontlab, Department of Neurology, AP_HP, Pitié-Salpêtrière University Hospital, Sorbonne Universities, Pierre et Marie Curie University, Paris 06, Paris, France;2. AXA Research Fund & UPMC Chair, Paris, France;3. University of British Columbia, Canada;4. Department of Neurology and Alzheimer Center, VU University Medical Center and Neuroscience Campus, Amsterdam, The Netherlands;5. University of Southern California San Diego, CA, USA;6. UMR1027, INSERM, Université Toulouse III, Toulouse University Hospital, France;7. IHU-A-ICM—Institut des Neurosciences translationnelles de Paris, Paris, France;8. INSERM U1146—CNRS UMR 7371—UPMC UM CR2, Site Pitié-Salpêtrière, Paris, France;9. Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), Institutes of Neurogenetics and Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany;10. School of Public Health, Faculty of Medicine, Imperial College London, London, UK;11. Clinical Neurochemistry Lab, Department of Neuroscience and Physiology, University of Gothenburg, Mölndal Hospital, Sahlgrenska University Hospital, Mölndal, Sweden;12. Federal Institute for Drugs and Medical Devices, Bonn, Germany;13. Laboratory of Alzheimer''s Neuroimaging and Epidemiology, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy;14. Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK;15. INSERM U 1219, Université de Bordeaux, France;p. University Pierre et Marie Curie, Assistance Publique des Hôpitaux de Paris, Alzheimer-Prion Team Institut du Cerveau et de la Moelle (ICM), Paris, France;q. University Hospitals and University of Geneva, Geneva, Switzerland;r. IRCCS Fatebenefratelli, Brescia, Italy;s. McGill Center for Studies in Aging, Douglas Mental Health Research Institute, Montreal, Canada;t. Fondation pour la Recherche sur Alzheimer, Hôpital Pitié-Salpêtrière, Paris, France;u. Department of Clinical Neurophysiology/MEG Center, VU University Medical Center, Amsterdam;v. Sorbonne Universités, UPMC Univ Paris 06, CNRS, INSERM, Laboratoire d''Imagerie Biomédicale, Paris, France;w. AP-HP, Hôpital Pitié-Salpêtrière, Département de Médecine Nucléaire, Paris, France;x. Department of Neurology, Washington University, Hope Center for Neurological Disorders, St. Louis, MO, USA;y. Department of Neurology, Washington University, Knight Alzheimer''s Disease Research Center, St. Louis, MO, USA;z. Center for Alzheimer Research, Karolinska Institutet, Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden;11. Institute of Clinical Medicine/ Neurology, University of Eastern Finland, Kuopio, Finland;12. Alzheimer''s Disease and Other Cognitive Disorders Unit, Hospital Clínic, Institut d''Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain;13. Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain;14. Center for Alzheimer''s & Neurodegenerative Disease Research, University of North Texas Health Science Center, TX, USA;15. Memory & Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA;16. Department of Molecular Imaging, Austin Health, University of Melbourne, Australia;17. Memory and Aging Program, Butler Hospital, Alpert Medical School of Brown University, USA;18. Department of Neurology, Alpert Medical School of Brown University, USA;19. Department of Psychiatry, Alpert Medical School of Brown University, USA;110. Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA;111. Harvard Medical School, Memory Disorders Unit, Center for Alzheimer Research and Treatment, Brigham and Women''s Hospital, Boston, USA;112. Harvard Medical School, Memory Disorders Unit, Center for Alzheimer Research and Treatment, Massachusetts General Hospital, Boston, USA;113. The Alzheimer''s Association Division of Medical & Scientific Relations, Chicago, USA;114. Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA;115. Department of Radiology, Mayo Clinic, Rochester MN, USA;1. Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA;2. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA;3. Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, USA;4. Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, USA;1. Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA;2. Veterans Affairs San Diego Healthcare System, San Diego, CA, USA;3. San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA;4. Department of Psychology, University of Southern California, Los Angeles, CA, USA;5. Department of Neurology, Drexel University, College of Medicine, Philadelphia, PA, USA;6. Department of Neurology, Boston University, School of Medicine, Boston, MA, USA;7. Framingham Heart Study, Boston University, School of Medicine, Boston, MA, USA;8. Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, CA, USA;1. Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA;2. Department of Radiology, Mayo Clinic, Rochester, MN, USA;3. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA;4. Department of Neurology, Mayo Clinic, Rochester, MN, USA;5. Division of Medical & Scientific Relations, Alzheimer''s Association, Chicago, IL, USA
Abstract:Here, we review progress by the Penn Biomarker Core in the Alzheimer's Disease Neuroimaging Initiative (ADNI) toward developing a pathological cerebrospinal fluid (CSF) and plasma biomarker signature for mild Alzheimer's disease (AD) as well as a biomarker profile that predicts conversion of mild cognitive impairment (MCI) and/or normal control subjects to AD. The Penn Biomarker Core also collaborated with other ADNI Cores to integrate data across ADNI to temporally order changes in clinical measures, imaging data, and chemical biomarkers that serve as mileposts and predictors of the conversion of normal control to MCI as well as MCI to AD, and the progression of AD. Initial CSF studies by the ADNI Biomarker Core revealed a pathological CSF biomarker signature of AD defined by the combination of Aβ1-42 and total tau (T-tau) that effectively delineates mild AD in the large multisite prospective clinical investigation conducted in ADNI. This signature appears to predict conversion from MCI to AD. Data fusion efforts across ADNI Cores generated a model for the temporal ordering of AD biomarkers which suggests that Aβ amyloid biomarkers become abnormal first, followed by changes in neurodegenerative biomarkers (CSF tau, F-18 fluorodeoxyglucose-positron emission tomography, magnetic resonance imaging) with the onset of clinical symptoms. The timing of these changes varies in individual patients due to genetic and environmental factors that increase or decrease an individual's resilience in response to progressive accumulations of AD pathologies. Further studies in ADNI will refine this model and render the biomarkers studied in ADNI more applicable to routine diagnosis and to clinical trials of disease modifying therapies.
Keywords:
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