Journal article
Alzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects
Brain (London, England : 1878), Vol.138(Pt 9), pp.2701-2715
09/2015
DOI: 10.1093/brain/awv199
PMCID: PMC4643624
PMID: 26220940
Abstract
In a large multicentre sample of cognitively normal subjects, as a function of age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer's disease biomarkers including: total tau, phosphorylated tau and amyloid-β1-42. Fifteen cohorts from 12 different centres with either enzyme-linked immunosorbent assays or Luminex® measurements were selected for this study. Each centre sent nine new cerebrospinal fluid aliquots that were used to measure total tau, phosphorylated tau and amyloid-β1-42 in the Gothenburg laboratory. Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40-84 years old). Amyloid-β amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer's disease cut-off values for cerebrospinal fluid amyloid-β1-42 and total tau, respectively. While gender did not affect these biomarker values, APOE genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that APOE ε4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-β1-42 values and APOE ε2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by APOE genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-β1-42 levels were already frequent in midlife and APOE genotype strongly affects the levels of cerebrospinal fluid amyloid-β1-42, phosphorylated tau and total tau across the lifespan without influencing the frequency of subjects with suspected non-amyloid pathology.
Details
- Title: Subtitle
- Alzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects
- Creators
- Jon B Toledo - 1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USAHenrik Zetterberg - 2 Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden 3 UCL Institute of Neurology, Department of Molecular Neuroscience, Queen Square, London, UKArgonde C van Harten - 4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The NetherlandsLidia Glodzik - 5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USAPablo Martinez-Lage - 6 Department of Neurology, Centre for Research and Advanced Therapies. Fundación CITA-Alzheimer Fundazioa, Donostia/San Sebastián, SpainLuisella Bocchio-Chiavetto - 7 IRCCS Centro San Giovanni di Dio FBF, Brescia, Italy 8 Faculty of Psychology, eCampus University, Novedrate (Como), ItalyLorena Rami - 9 Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic i Universitari, Barcelona, SpainOskar Hansson - 10 Department of Clinical Sciences, Lund University, Lund, Sweden 11 Memory clinic, Skåne University Hospital, Lund, SwedenReisa Sperling - 11 Memory clinic, Skåne University Hospital, Lund, SwedenSebastiaan Engelborghs - 13 Department of Neurology and Memory Clinic, Hospital Network Antwerp, Middelheim and Hoge Beuken, Belgium 14 Reference Centre for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Institute Born-Bunge, University of Antwerp, Antwerp, BelgiumRicardo S Osorio - 5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USAHugo Vanderstichele - 15 ADx NeuroSciences, Technologiepark 4, Gent, BelgiumManu Vandijck - 16 Fujirebio Europe nv, Technologiepark 6, Gent, BelgiumHarald Hampel - 17 AXA Research Fund and UPMC, Université Pierre et Marie Curie, Paris, France 18 Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A) & Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, FranceStefan Teipl - 19 Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany 20 DZNE, German Centre for Neurodegenerative Diseases, Rostock, GermanyAbhay Moghekar - 21 Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USAMarilyn Albert - 21 Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USAWilliam T Hu - 22 Department of Neurology, Emory University School of Medicine, Atlanta, GA, USAJose A Monge Argilés - 23 Department of Neurology, University General Hospital of Alicante, Alicante, SpainAna Gorostidi - 24 Neuroscience Unit, Biodonostia Research Institute, San Sebastian, SpainCharlotte E Teunissen - 25 Neurochemistry Lab and Biobank, Dept. of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, The NetherlandsPeter P De Deyn - 13 Department of Neurology and Memory Clinic, Hospital Network Antwerp, Middelheim and Hoge Beuken, Belgium 14 Reference Centre for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Institute Born-Bunge, University of Antwerp, Antwerp, BelgiumBradley T Hyman - 12 Massachusetts Alzheimer's Disease Research Centre, Harvard Aging Brain Study, Department of Neurology; Massachusetts General Hospital, Harvard Medical School, Boston, MA,USAJose L Molinuevo - 9 Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic i Universitari, Barcelona, SpainGiovanni B Frisoni - 7 IRCCS Centro San Giovanni di Dio FBF, Brescia, Italy 26 University Hospitals and University of Geneva, Geneva, SwitzerlandGurutz Linazasoro - 6 Department of Neurology, Centre for Research and Advanced Therapies. Fundación CITA-Alzheimer Fundazioa, Donostia/San Sebastián, SpainMony J de Leon - 5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USAWiesje M van der Flier - 4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands 27 Department of Epidemiology/Biostatistics, VU University Medical Centre, USAPhilip Scheltens - 4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The NetherlandsKaj Blennow - 2 Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden 27 Department of Epidemiology/Biostatistics, VU University Medical Centre, USALeslie M Shaw - 1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USAJohn Q Trojanowski - 1 Department of Pathology and Laboratory Medicine, Institute on Aging, Centre for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA trojanow@mail.med.upenn.eduAlzheimer’s Disease Neuroimaging Initiative
- Contributors
- Laura L Boles-Ponto (Contributor) - University of Iowa, Radiology
- Resource Type
- Journal article
- Publication Details
- Brain (London, England : 1878), Vol.138(Pt 9), pp.2701-2715
- Publisher
- England
- DOI
- 10.1093/brain/awv199
- PMID
- 26220940
- PMCID
- PMC4643624
- ISSN
- 0006-8950
- eISSN
- 1460-2156
- Grant note
- R01 AG022374 / NIA NIH HHS AG022374 / NIA NIH HHS R21 AG043885 / NIA NIH HHS P01 AG032953 / NIA NIH HHS AG13616 / NIA NIH HHS CIHR P50 AG005146 / NIA NIH HHS P50 AG016976 / NIA NIH HHS P30 AG013846 / NIA NIH HHS R01 HL118624 / NHLBI NIH HHS P01 AG017586 / NIA NIH HHS U01 AG024904 / NIA NIH HHS P30 AG008051 / NIA NIH HHS P01 AG036694 / NIA NIH HHS P50 AG005134 / NIA NIH HHS U19 AG033655 / NIA NIH HHS P50 NS053488 / NINDS NIH HHS K23 AG042856 / NIA NIH HHS UL1 TR001079 / NCATS NIH HHS AG1210 / NIA NIH HHS
- Language
- English
- Date published
- 09/2015
- Academic Unit
- Radiology; Pharmaceutical Sciences and Experimental Therapeutics; Nursing
- Record Identifier
- 9984051799402771
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