Alberto Lleó1, Daniel Alcolea2, Pablo Martínez-Lage3, Philip Scheltens4, Lucilla Parnetti5, Judes Poirier6, Anja H Simonsen7, Marcel M Verbeek8, Pedro Rosa-Neto6, Rosalinde E R Slot4, Mikel Tainta3, Andrea Izaguirre3, Babette L R Reijs9, Lucia Farotti5, Magda Tsolaki10, Rik Vandenbergue11, Yvonne Freund-Levi12, Frans R J Verhey9, Jordi Clarimón2, Juan Fortea2, Lutz Frolich13, Isabel Santana14, José Luis Molinuevo15, Sylvain Lehmann16, Pieter J Visser17, Charlotte E Teunissen4, Henrik Zetterberg18, Kaj Blennow19. 1. Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Centre of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Madrid, Spain. Electronic address: alleo@santpau.es. 2. Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; 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; Department of Laboratory Medicine, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Nijmegen, the Netherlands. 9. Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands. 10. 1st Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Makedonia, Greece; Alzheimer Hellas, Thessaloniki, Greece. 11. University Hospital Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium. 12. 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. 13. Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany. 14. Dementia Clinic, Centro Hospitalar e Universitário de Coimbra and Faculty of Medicine, Universidade de Coimbra, Coimbra, Portugal. 15. ICN Hospital Clinic i Universitari, Barcelona, Spain. 16. Univ Montpellier, CHU Montpellier, Montpellier, France. 17. Amsterdam UMC, Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands. 18. Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, University College London, Queen Square, London, United Kingdom; UK Dementia Research Institute at UCL, London, United Kingdom. 19. Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Abstract
INTRODUCTION: Within-person trajectories of cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD) are not well defined. METHODS: We included 467 subjects from the BIOMARKAPD study with at least two serial CSF samples. Diagnoses were subjective cognitive decline (n = 75), mild cognitive impairment (n = 128), and AD dementia (n = 110), and a group of cognitively unimpaired subjects (n = 154) were also included. We measured baseline and follow-up CSF levels of total tau (t-tau), phosphorylated tau (p-tau), YKL-40, and neurofilament light (NfL). Median CSF sampling interval was 2.1 years. RESULTS: CSF levels of t-tau, p-tau, NfL, and YKL-40 were 2% higher per each year of baseline age in controls (P <.001). In AD, t-tau levels were 1% lower (P <.001) and p-tau levels did not change per each year of baseline age. Longitudinally, only NfL (P <.001) and YKL-40 (P <.02) increased during the study period. DISCUSSION: All four CSF biomarkers increase with age, but this effect deviates in AD for t-tau and p-tau.
INTRODUCTION: Within-person trajectories of cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD) are not well defined. METHODS: We included 467 subjects from the BIOMARKAPD study with at least two serial CSF samples. Diagnoses were subjective cognitive decline (n = 75), mild cognitive impairment (n = 128), and AD dementia (n = 110), and a group of cognitively unimpaired subjects (n = 154) were also included. We measured baseline and follow-up CSF levels of total tau (t-tau), phosphorylated tau (p-tau), YKL-40, and neurofilament light (NfL). Median CSF sampling interval was 2.1 years. RESULTS: CSF levels of t-tau, p-tau, NfL, and YKL-40 were 2% higher per each year of baseline age in controls (P <.001). In AD, t-tau levels were 1% lower (P <.001) and p-tau levels did not change per each year of baseline age. Longitudinally, only NfL (P <.001) and YKL-40 (P <.02) increased during the study period. DISCUSSION: All four CSF biomarkers increase with age, but this effect deviates in AD for t-tau and p-tau.
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