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Alzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects.

  • Toledo JB 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.
  • Zetterberg H 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, UK.
  • van Harten AC 4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
  • Glodzik L 5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA.
  • Martinez-Lage P 6 Department of Neurology, Centre for Research and Advanced Therapies. Fundación CITA-Alzheimer Fundazioa, Donostia/San Sebastián, Spain.
  • Bocchio-Chiavetto L 7 IRCCS Centro San Giovanni di Dio FBF, Brescia, Italy 8 Faculty of Psychology, eCampus University, Novedrate (Como), Italy.
  • Rami L 9 Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic i Universitari, Barcelona, Spain.
  • Hansson O 10 Department of Clinical Sciences, Lund University, Lund, Sweden 11 Memory clinic, Skåne University Hospital, Lund, Sweden.
  • Sperling R 11 Memory clinic, Skåne University Hospital, Lund, Sweden.
  • Engelborghs S 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, Belgium.
  • Osorio RS 5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA.
  • Vanderstichele H 15 ADx NeuroSciences, Technologiepark 4, Gent, Belgium.
  • Vandijck M 16 Fujirebio Europe nv, Technologiepark 6, Gent, Belgium.
  • Hampel H 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, France.
  • Teipl S 19 Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany 20 DZNE, German Centre for Neurodegenerative Diseases, Rostock, Germany.
  • Moghekar A 21 Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Albert M 21 Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Hu WT 22 Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
  • Monge Argilés JA 23 Department of Neurology, University General Hospital of Alicante, Alicante, Spain.
  • Gorostidi A 24 Neuroscience Unit, Biodonostia Research Institute, San Sebastian, Spain.
  • Teunissen CE 25 Neurochemistry Lab and Biobank, Dept. of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands.
  • De Deyn PP 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, Belgium.
  • Hyman BT 12 Massachusetts Alzheimer's Disease Research Centre, Harvard Aging Brain Study, Department of Neurology; Massachusetts General Hospital, Harvard Medical School, Boston, MA,USA.
  • Molinuevo JL 9 Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic i Universitari, Barcelona, Spain.
  • Frisoni GB 7 IRCCS Centro San Giovanni di Dio FBF, Brescia, Italy 26 University Hospitals and University of Geneva, Geneva, Switzerland.
  • Linazasoro G 6 Department of Neurology, Centre for Research and Advanced Therapies. Fundación CITA-Alzheimer Fundazioa, Donostia/San Sebastián, Spain.
  • de Leon MJ 5 Centre for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA.
  • van der Flier WM 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, USA.
  • Scheltens P 4 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
  • Blennow K 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, USA.
  • Shaw LM 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.
  • Trojanowski JQ 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.edu.
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  • 2015-07-30
Published in:
  • Brain : a journal of neurology. - 2015
Alzheimer’s disease
biomarkers
cognitive ageing
dementia
imaging
Adult
Age Factors
Aged
Aged, 80 and over
Alzheimer Disease
Amyloid beta-Peptides
Analysis of Variance
Apolipoproteins E
Cognition
Cohort Studies
Female
Humans
Male
Middle Aged
Neurodegenerative Diseases
Neuropsychological Tests
Peptide Fragments
Severity of Illness Index
tau Proteins
English 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.
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  • English
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bronze
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https://sonar.ch/global/documents/46441
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