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

Alberto Lleó; Daniel Alcolea; Pablo Martínez-Lage; Philip Scheltens; Lucilla Parnetti; Judes Poirier; Anja H. Simonsen; Marcel M. Verbeek; Pedro Rosa-Neto; Rosalinde E. R. Slot; Mikel Tainta; Andrea Izaguirre; Babette L. R. Reijs; Lucia Farotti; Magda Tsolaki; Rik Vandenbergue; Yvonne Freund-Levi; Frans R. J. Verhey; Jordi Clarimón; Juan Fortea; Lutz Frolich; Isabel Santana; José Luis Molinuevo; Sylvain Lehmann; Pieter J. Visser; Charlotte E. Teunissen; Henrik Zetterberg; Kaj Blennow

doi:10.1016/j.jalz.2019.01.015

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

Alberto Lleó
, Daniel Alcolea
, Pablo Martínez-Lage
, Philip Scheltens
, Lucilla Parnetti
, Judes Poirier
, Anja H. Simonsen
, Marcel M. Verbeek
, Pedro Rosa-Neto
, Rosalinde E. R. Slot
, Mikel Tainta
, Andrea Izaguirre
, Babette L. R. Reijs
, Lucia Farotti
, Magda Tsolaki
, Rik Vandenbergue
, Yvonne Freund-Levi
, Frans R. J. Verhey
, Jordi Clarimón
, Juan Fortea

Lutz Frolich, Isabel Santana, José Luis Molinuevo, Sylvain Lehmann, Pieter J. Visser, Charlotte E. Teunissen, Henrik Zetterberg, Kaj Blennow

Autonomous University of Barcelona
CIBER - Center for Biomedical Research Network
Center for Research and Advanced Therapies, San Sebastian, Spain
University of Perugia
Douglas Mental Health University Institute
University of Copenhagen
Radboud University Nijmegen
Maastricht University
Aristotle University of Thessaloniki
Alzheimer Hellas, Thessaloniki, Greece
KU Leuven
King's College London
Ruprecht-Karls-University
Centro Hospitalar e Universitário de Coimbra
Hospital Clinic de Barcelona
CHU Montpellier
Sahlgrenska Academy
University of Gothenburg
Great Ormond St Hospital for Children NHS Trust

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	742-753
Number of pages	12
Journal	Alzheimer's and Dementia
Volume	15
Issue number	6
DOIs	https://doi.org/10.1016/j.jalz.2019.01.015
Publication status	Published - 1 Jun 2019

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Alzheimer
Amyloid
CSF
Inflammation
Neurofilaments
Tau
YKL-40

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10.1016/j.jalz.2019.01.015

Longitudinal-cerebrospinal-fluid-biomarker-trajectories-along-the-alzheimers-disease-continuum-in-the-biomarkapd-study.pdfFinal published version, 3.48 MBLicence: Taverne

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Lleó, A., Alcolea, D., Martínez-Lage, P., Scheltens, P., Parnetti, L., Poirier, J., Simonsen, A. H., Verbeek, M. M., Rosa-Neto, P., Slot, R. E. R., Tainta, M., Izaguirre, A., Reijs, B. L. R., Farotti, L., Tsolaki, M., Vandenbergue, R., Freund-Levi, Y., Verhey, F. R. J., Clarimón, J., ... Blennow, K. (2019). Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study. Alzheimer's and Dementia, 15(6), 742-753. https://doi.org/10.1016/j.jalz.2019.01.015

@article{430f502456394ffc8f8b4394f84283b9,

title = "Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study",

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.",

keywords = "Alzheimer, Amyloid, CSF, Inflammation, Neurofilaments, Tau, YKL-40",

author = "Alberto Lle{\'o} and Daniel Alcolea and Pablo Mart{\'i}nez-Lage and Philip Scheltens and Lucilla Parnetti and Judes Poirier and Simonsen, \{Anja H.\} and Verbeek, \{Marcel M.\} and Pedro Rosa-Neto and Slot, \{Rosalinde E. R.\} and Mikel Tainta and Andrea Izaguirre and Reijs, \{Babette L. R.\} and Lucia Farotti and Magda Tsolaki and Rik Vandenbergue and Yvonne Freund-Levi and Verhey, \{Frans R. J.\} and Jordi Clarim{\'o}n and Juan Fortea and Lutz Frolich and Isabel Santana and Molinuevo, \{Jos{\'e} Luis\} and Sylvain Lehmann and Visser, \{Pieter J.\} and Teunissen, \{Charlotte E.\} and Henrik Zetterberg and Kaj Blennow",

year = "2019",

month = jun,

day = "1",

doi = "10.1016/j.jalz.2019.01.015",

language = "English",

volume = "15",

pages = "742--753",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Elsevier",

number = "6",

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Lleó, A, Alcolea, D, Martínez-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, Clarimón, J, Fortea, J, Frolich, L, Santana, I, Molinuevo, JL, Lehmann, S, Visser, PJ , Teunissen, CE, Zetterberg, H & Blennow, K 2019, 'Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study', Alzheimer's and Dementia, vol. 15, no. 6, pp. 742-753. https://doi.org/10.1016/j.jalz.2019.01.015

TY - JOUR

T1 - Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study

AU - Lleó, Alberto

AU - Alcolea, Daniel

AU - Martínez-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 - Clarimón, Jordi

AU - Fortea, Juan

AU - Frolich, Lutz

AU - Santana, Isabel

AU - Molinuevo, José Luis

AU - Lehmann, Sylvain

AU - Visser, Pieter J.

AU - Teunissen, Charlotte E.

AU - Zetterberg, Henrik

AU - Blennow, Kaj

PY - 2019/6/1

Y1 - 2019/6/1

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 (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.

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 (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.

KW - Alzheimer

KW - Amyloid

KW - CSF

KW - Inflammation

KW - Neurofilaments

KW - Tau

KW - YKL-40

UR - https://www.scopus.com/pages/publications/85063904370

UR - https://www.ncbi.nlm.nih.gov/pubmed/30967340

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 and Dementia

JF - Alzheimer's and Dementia

IS - 6

ER -

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

Abstract

UN SDGs

Keywords

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