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Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study

Journal article
Authors A. Lleó
D. Alcolea
P. Martínez-Lage
P. Scheltens
L. Parnetti
J. Poirier
A. H. Simonsen
M. M. Verbeek
P. Rosa-Neto
R. E. R. Slot
M. Tainta
A. Izaguirre
B. L. R. Reijs
L. Farotti
M. Tsolaki
R. Vandenbergue
Y. Freund-Levi
F. R. J. Verhey
J. Clarimón
J. Fortea
L. Frolich
I. Santana
J. L. Molinuevo
S. Lehmann
P. J. Visser
C. E. Teunissen
Henrik Zetterberg
Kaj Blennow
Published in Alzheimer's and Dementia
Volume 15
Issue 6
Pages 742-753
ISSN 1552-5260
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 742-753
Language en
Keywords Alzheimer, Amyloid, CSF, Inflammation, Neurofilaments, Tau, YKL-40
Subject categories Neurosciences


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. © 2019 the Alzheimer's Association

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