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
Discussion: All four CSF biomarkers increase with age, but this effect deviates in AD for t-tau and ptau. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
| Original language | English |
|---|---|
| Pages (from-to) | 742-753 |
| Number of pages | 12 |
| Journal | Alzheimer's & Dementia |
| Volume | 15 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2019 |
Keywords
- ASSOCIATION WORKGROUPS
- Alzheimer
- Amyloid
- BETA
- CSF
- CSF BIOMARKERS
- DEMENTIA
- DIAGNOSTIC GUIDELINES
- Inflammation
- NATIONAL INSTITUTE
- NEUROFILAMENT LIGHT
- Neurofilaments
- PROTEIN
- RECOMMENDATIONS
- TAU LEVELS
- Tau
- YKL-40
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In: Alzheimer's & Dementia, Vol. 15, No. 6, 06.2019, p. 742-753.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study
AU - Lleo, Alberto
AU - Alcolea, Daniel
AU - Martinez-Lage, Pablo
AU - Scheltens, Philip
AU - Parnetti, Lucilla
AU - Poirier, Judes
AU - Simonsen, Anja H.
AU - Verbeek, Marcel M.
AU - Rosa-Neto, Pedro
AU - Slot, Rosalinde E. R.
AU - Tainta, Mikel
AU - Izaguirre, Andrea
AU - Reijs, Babette L. R.
AU - Farotti, Lucia
AU - Tsolaki, Magda
AU - Vandenbergue, Rik
AU - Freund-Levi, Yvonne
AU - Verhey, Frans R. J.
AU - Clarimon, Jordi
AU - Fortea, Juan
AU - Frolich, Lutz
AU - Santana, Isabel
AU - Luis Molinuevo, Jose
AU - Lehmann, Sylvain
AU - Visser, Pieter J.
AU - Teunissen, Charlotte E.
AU - Zetterberg, Henrik
AU - Blennow, Kaj
N1 - Funding Information: This manuscript is based on an EU Joint Program Neurodegenerative Disease Research (JPND) Project ( www.jpnd.eu ). The Project is supported thorough the following funding organizations under the aegis of JPND: the Italian Ministry of Health ; the Netherlands Organization for Health, Research and Development (ZonMw); The Instituto de Salud Carlos III (PI14/1561 and PI17/1895 to A.L. and CIBERNED), Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, “Una manera de hacer Europa”; the Bundesministerium für Bildung und Forschung (BMBF), Germany; and the Swedish Research Council . Innovation Fund Denmark (grant no.: 0603-00470B to A.H.S) and Fonds de Recherche du Québec–Santé (FRQS), the J. L. Lévesque Foundation. The CITA-alzheimer study is partially funded by the Department of Health of the Basque Government (2016111096); the Carlos III Institute of Health (PI15/00919, PN de I + D + I 2013-2016); and “Obra Social Kutxa Fundazioa”. H.Z. is a Wallenberg Academy Fellow, and his contribution was further supported in part by grants from the European Research Council (#681712) and the Swedish Research Council (#2013-2546). K.B. is supported by the Torsten Söderberg Foundation at the Royal Swedish Academy of Sciences . The EDAR study was funded by the European Commission as part of the 6th Framework Program (contract # 37670). Fujirebio Europe provided INNO-BIA AlzBio3 kits in kind. Funding Information: Conflict of interest statement: A.L. has served at the scientific advisory boards of Fujirebio Europe, Eli Lilly, Novartis, and Nutricia and is the inventor of a patent on synaptic markers in cerebrospinal fluid. D.A. has served at scientific advisory boards of Fujirebio Europe, Nutricia and Roche. L.P. has received honoraria as a member of advisory boards from Fujirebio Europe, IBL International, Merck, Roche, and Biogen. L.F. has been a part of the advisory board of Allergan, Eli Lilly, Avraham Pharmaceuticals, Axon Neuroscience, Axovant, Biogen, Boehringer Ingelheim, Eisai, Functional Neuromodulation, Lundbeck, Merck Sharp & Dohme, Novartis, Pfizer, Pharnext, Roche, and Schwabe and has received a research grant from Novartis . J.L.M. has served as a consultant or at advisory boards for Axovant, Biogen, Genentech, Eisai, Eli Lilly, IBL International, Lundbeck, Merck, Novartis, Pfizer, Roche and Roche Diagnostics, Oryzon, Raman Health, Green Valley, and Allergan. H.Z. has served at the scientific advisory boards of Eli Lilly, Roche Diagnostics, Wave, and Cellectricon; has received travel support from Teva; and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures–based platform company at the University of Gothenburg. K.B. has served as a consultant or at advisory boards for Alzheon, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Merck, Novartis, Pfizer, and Roche Diagnostics and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. Funding Information: Conflict of interest statement: A.L. has served at the scientific advisory boards of Fujirebio Europe, Eli Lilly, Novartis, and Nutricia and is the inventor of a patent on synaptic markers in cerebrospinal fluid. D.A. has served at scientific advisory boards of Fujirebio Europe, Nutricia and Roche. L.P. has received honoraria as a member of advisory boards from Fujirebio Europe, IBL International, Merck, Roche, and Biogen. L.F. has been a part of the advisory board of Allergan, Eli Lilly, Avraham Pharmaceuticals, Axon Neuroscience, Axovant, Biogen, Boehringer Ingelheim, Eisai, Functional Neuromodulation, Lundbeck, Merck Sharp & Dohme, Novartis, Pfizer, Pharnext, Roche, and Schwabe and has received a research grant from Novartis. J.L.M. has served as a consultant or at advisory boards for Axovant, Biogen, Genentech, Eisai, Eli Lilly, IBL International, Lundbeck, Merck, Novartis, Pfizer, Roche and Roche Diagnostics, Oryzon, Raman Health, Green Valley, and Allergan. H.Z. has served at the scientific advisory boards of Eli Lilly, Roche Diagnostics, Wave, and Cellectricon; has received travel support from Teva; and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures–based platform company at the University of Gothenburg. K.B. has served as a consultant or at advisory boards for Alzheon, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Merck, Novartis, Pfizer, and Roche Diagnostics and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg.This manuscript is based on an EU Joint Program Neurodegenerative Disease Research (JPND) Project (www.jpnd.eu). The Project is supported thorough the following funding organizations under the aegis of JPND: the Italian Ministry of Health; the Netherlands Organization for Health, Research and Development (ZonMw); The Instituto de Salud Carlos III (PI14/1561 and PI17/1895 to A.L. and CIBERNED), Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, “Una manera de hacer Europa”; the Bundesministerium für Bildung und Forschung (BMBF), Germany; and the Swedish Research Council. Innovation Fund Denmark (grant no.: 0603-00470B to A.H.S) and Fonds de Recherche du Québec–Santé (FRQS), the J. L. Lévesque Foundation. The CITA-alzheimer study is partially funded by the Department of Health of the Basque Government (2016111096); the Carlos III Institute of Health (PI15/00919, PN de I + D + I 2013-2016); and “Obra Social Kutxa Fundazioa”. H.Z. is a Wallenberg Academy Fellow, and his contribution was further supported in part by grants from the European Research Council (#681712) and the Swedish Research Council (#2013-2546). K.B. is supported by the Torsten Söderberg Foundation at the Royal Swedish Academy of Sciences. The EDAR study was funded by the European Commission as part of the 6th Framework Program (contract # 37670). Fujirebio Europe provided INNO-BIA AlzBio3 kits in kind. Conflict of interest statement: A.L. has served at the scientific advisory boards of Fujirebio Europe, Eli Lilly, Novartis, and Nutricia and is the inventor of a patent on synaptic markers in cerebrospinal fluid. D.A. has served at scientific advisory boards of Fujirebio Europe, Nutricia and Roche. L.P. has received honoraria as a member of advisory boards from Fujirebio Europe, IBL International, Merck, Roche, and Biogen. L.F. has been a part of the advisory board of Allergan, Eli Lilly, Avraham Pharmaceuticals, Axon Neuroscience, Axovant, Biogen, Boehringer Ingelheim, Eisai, Functional Neuromodulation, Lundbeck, Merck Sharp & Dohme, Novartis, Pfizer, Pharnext, Roche, and Schwabe and has received a research grant from Novartis. J.L.M. has served as a consultant or at advisory boards for Axovant, Biogen, Genentech, Eisai, Eli Lilly, IBL International, Lundbeck, Merck, Novartis, Pfizer, Roche and Roche Diagnostics, Oryzon, Raman Health, Green Valley, and Allergan. H.Z. has served at the scientific advisory boards of Eli Lilly, Roche Diagnostics, Wave, and Cellectricon; has received travel support from Teva; and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures–based platform company at the University of Gothenburg. K.B. has served as a consultant or at advisory boards for Alzheon, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Merck, Novartis, Pfizer, and Roche Diagnostics and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. Funding Information: Conflict of interest statement: A.L. has served at the scientific advisory boards of Fujirebio Europe, Eli Lilly, Novartis, and Nutricia and is the inventor of a patent on synaptic markers in cerebrospinal fluid. D.A. has served at scientific advisory boards of Fujirebio Europe, Nutricia and Roche. L.P. has received honoraria as a member of advisory boards from Fujirebio Europe, IBL International, Merck, Roche, and Biogen. L.F. has been a part of the advisory board of Allergan, Eli Lilly, Avraham Pharmaceuticals, Axon Neuroscience, Axovant, Biogen, Boehringer Ingelheim, Eisai, Functional Neuromodulation, Lundbeck, Merck Sharp & Dohme, Novartis, Pfizer, Pharnext, Roche, and Schwabe and has received a research grant from Novartis. J.L.M. has served as a consultant or at advisory boards for Axovant, Biogen, Genentech, Eisai, Eli Lilly, IBL International, Lundbeck, Merck, Novartis, Pfizer, Roche and Roche Diagnostics, Oryzon, Raman Health, Green Valley, and Allergan. H.Z. has served at the scientific advisory boards of Eli Lilly, Roche Diagnostics, Wave, and Cellectricon; has received travel support from Teva; and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures?based platform company at the University of Gothenburg. K.B. has served as a consultant or at advisory boards for Alzheon, BioArctic, Biogen, Eli Lilly, Fujirebio Europe, IBL International, Merck, Novartis, Pfizer, and Roche Diagnostics and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg.This manuscript is based on an EU Joint Program Neurodegenerative Disease Research (JPND) Project (www.jpnd.eu). The Project is supported thorough the following funding organizations under the aegis of JPND: the Italian Ministry of Health; the Netherlands Organization for Health, Research and Development (ZonMw); The Instituto de Salud Carlos III (PI14/1561 and PI17/1895 to A.L. and CIBERNED), Fondo Europeo de Desarrollo Regional (FEDER), Uni?n Europea, ?Una manera de hacer Europa?; the Bundesministerium f?r Bildung und Forschung (BMBF), Germany; and the Swedish Research Council. Innovation Fund Denmark (grant no.: 0603-00470B to A.H.S) and Fonds de Recherche du Qu?bec?Sant? (FRQS), the J. L. L?vesque Foundation. The CITA-alzheimer study is partially funded by the Department of Health of the Basque Government (2016111096); the Carlos III Institute of Health (PI15/00919, PN de I + D + I 2013-2016); and ?Obra Social Kutxa Fundazioa?. H.Z. is a Wallenberg Academy Fellow, and his contribution was further supported in part by grants from the European Research Council (#681712) and the Swedish Research Council (#2013-2546). K.B. is supported by the Torsten S?derberg Foundation at the Royal Swedish Academy of Sciences. The EDAR study was funded by the European Commission as part of the 6th Framework Program (contract # 37670). Fujirebio Europe provided INNO-BIA AlzBio3 kits in kind. Publisher Copyright: © 2019 the Alzheimer's Association
PY - 2019/6
Y1 - 2019/6
N2 - 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 (PDiscussion: All four CSF biomarkers increase with age, but this effect deviates in AD for t-tau and ptau. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
AB - 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 (PDiscussion: All four CSF biomarkers increase with age, but this effect deviates in AD for t-tau and ptau. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
KW - ASSOCIATION WORKGROUPS
KW - Alzheimer
KW - Amyloid
KW - BETA
KW - CSF
KW - CSF BIOMARKERS
KW - DEMENTIA
KW - DIAGNOSTIC GUIDELINES
KW - Inflammation
KW - NATIONAL INSTITUTE
KW - NEUROFILAMENT LIGHT
KW - Neurofilaments
KW - PROTEIN
KW - RECOMMENDATIONS
KW - TAU LEVELS
KW - Tau
KW - YKL-40
U2 - 10.1016/j.jalz.2019.01.015
DO - 10.1016/j.jalz.2019.01.015
M3 - Article
C2 - 30967340
SN - 1552-5260
VL - 15
SP - 742
EP - 753
JO - Alzheimer's & Dementia
JF - Alzheimer's & Dementia
IS - 6
ER -