Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD studyCentre for Memory Disturbances, Section of Neurology, Lab of Clinical Neurochemistry, University of Perugia, Perugia, Italy.
Centre for the Studies on the Prevention of Alzheimer's Disease, Douglas Mental Health University Institute, Montréal, QC, Canada.
Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
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.
Centre for the Studies on the Prevention of Alzheimer's Disease, Douglas Mental Health University Institute, Montréal, QC, Canada.
Amsterdam UMC, Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
Center for Research and Advanced Therapies, Fundación CITA-alzheimer Fundazioa, San Sebastian, Spain.
Center for Research and Advanced Therapies, Fundación CITA-alzheimer Fundazioa, San Sebastian, Spain.
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
Centre for Memory Disturbances, Section of Neurology, Lab of Clinical Neurochemistry, University of Perugia, Perugia, Italy.
1st Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Makedonia, Greece; Alzheimer Hellas, Thessaloniki, Greece.
University Hospital Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
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.
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.
Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Dementia Clinic, Centro Hospitalar e Universitário de Coimbra and Faculty of Medicine, Universidade de Coimbra, Coimbra, Portugal.
ICN Hospital Clinic i Universitari, Barcelona, Spain.
Univ Montpellier, CHU Montpellier, Montpellier, France.
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.
Amsterdam UMC, Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
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.
Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
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2019 (English)In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 15, no 6, p. 742-753Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 15, no 6, p. 742-753
Keywords [en]
Alzheimer, Amyloid, CSF, Inflammation, Neurofilaments, Tau, YKL-40
National Category
Medical and Health Sciences Neurology
Identifiers
URN: urn:nbn:se:oru:diva-79152DOI: 10.1016/j.jalz.2019.01.015ISI: 000470084500002PubMedID: 30967340Scopus ID: 2-s2.0-85063904370OAI: oai:DiVA.org:oru-79152DiVA, id: diva2:1385393
Funder
Swedish Research CouncilEU, European Research Council, 681712
Note
Funding Agencies:
Ministry of Health, Italy, Appeared in article as Italian Ministry of Health
Netherlands Organization for Health Research and Development, Appeared in article as Netherlands Organization for Health, Research and Development (ZonMw)
Instituto de Salud Carlos III, Appeared in article as Instituto de Salud Carlos III, Grant numbers PI14/1561, PI17/1895
Fondo Europeo de Desarrollo Regional (FEDER), Union Europea, "Una manera de hacer Europa"
Federal Ministry of Education & Research (BMBF), Appeared in article as Bundesministerium fur Bildung und Forschung (BMBF), Germany
Swedish Research Council, Appeared in article as Swedish Research Council
Innovation Fund Denmark, Grant number 0603-00470B
Fonds de Recherche du Quebec-Sante (FRQS)
J. L. Levesque Foundation
Department of Health of the Basque Government, Grant number 2016111096
Instituto de Salud Carlos III, Appeared in article as Carlos III Institute of Health, Grant number PI15/00919
"Obra Social Kutxa Fundazioa"
European Research Council (ERC), Appeared in article as European Research Council, Grant number 681712
Swedish Research Council, Appeared in article as Swedish Research Council, Grant number 2013-2546
Torsten Soderberg Foundation at the Royal Swedish Academy of Sciences
European Union (EU), Appeared in article as European Commission as part of the 6th Framework Program, Grant number 37670
2020-01-142020-01-142023-03-28Bibliographically approved