Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study
Por:
Lleo, A, Alcolea, D, Martinez-Lage, P, Scheltens, P, Parnetti, L, Poirier, J, Simonsen, AH, Verbeek, MM, Rosa-Neto, P, Slot, RER, Tainta, M, Izaguirre, A, Reijs, BLR, Farotti, L, Tsolaki, M, Vandenbergue, R, Freund-Levi, Y, Verhey, FRJ, Clarimon, J, Fortea, J, Frolich, L, Santana, I, Molinuevo, JL, Lehmann, S, Visser, PJ, Teunissen, CE, Zetterberg, H, Blennow, K
Publicada:
1 jun 2019
Resumen:
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 ptau. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Filiaciones:
Lleo, A:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Alcolea, D:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Martinez-Lage, P:
Fdn CITA Alzheimer Fundazioa, Ctr Res & Adv Therapies, San Sebastian, Spain
Scheltens, P:
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam UMC, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Parnetti, L:
Univ Perugia, Sect Neurol, Lab Clin Neurochem, Ctr Memory Disturbances, Perugia, Italy
Poirier, J:
Douglas Mental Hlth Univ Inst, Ctr Studies Prevent Alzheimers Dis, Montreal, PQ, Canada
Simonsen, AH:
Univ Copenhagen, Danish Dementia Res Ctr, Rigshosp, Copenhagen, Denmark
Verbeek, MM:
Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol,Radboud Alzheimer Ctr, Nijmegen, Netherlands
Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Lab Med,Radboud Alzheimer Ctr, Nijmegen, Netherlands
Rosa-Neto, P:
Douglas Mental Hlth Univ Inst, Ctr Studies Prevent Alzheimers Dis, Montreal, PQ, Canada
Slot, RER:
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam UMC, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Tainta, M:
Fdn CITA Alzheimer Fundazioa, Ctr Res & Adv Therapies, San Sebastian, Spain
Izaguirre, A:
Fdn CITA Alzheimer Fundazioa, Ctr Res & Adv Therapies, San Sebastian, Spain
Reijs, BLR:
Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
Farotti, L:
Univ Perugia, Sect Neurol, Lab Clin Neurochem, Ctr Memory Disturbances, Perugia, Italy
Tsolaki, M:
Aristotle Univ Thessaloniki, AHEPA Univ Hosp, Dept Neurol 1, Macedonia, Greece
Alzheimer Hellas, Thessaloniki, Greece
Vandenbergue, R:
Univ Hosp Leuven, Leuven, Belgium
Katholieke Univ Leuven, Dept Neurosci, Lab Cognit Neurol, Leuven, Belgium
Freund-Levi, Y:
Karolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, Huddinge, Sweden
Kings Coll London, Dept Old Age Psychiat Psychol & Neurosci, London, England
Verhey, FRJ:
Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
Clarimon, J:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fortea, J:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Frolich, L:
Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Mannheim, Germany
Santana, I:
Ctr Hosp & Univ Coimbra, Dementia Clin, Coimbra, Portugal
Univ Coimbra, Fac Med, Coimbra, Portugal
Molinuevo, JL:
ICN Hosp Clin & Univ, Barcelona, Spain
Lehmann, S:
Univ Montpellier, CHU Montpellier, Montpellier, France
Visser, PJ:
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam UMC, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Maastricht Univ, Alzheimer Ctr Limburg, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
Teunissen, CE:
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam UMC, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands
Zetterberg, H:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Molndal, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
UCL, Dept Neurodegenerat Dis, Queen Sq, London, England
UCL, UK Dementia Res Inst, London, England
Blennow, K:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Molndal, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
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