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

Department of Neurology

102 Citations (Scopus)

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
Journal	Alzheimer's & dementia : the journal of the Alzheimer's Association
Volume	15
Issue number	6
Pages (from-to)	742-753
Number of pages	12
ISSN	1552-5260
DOIs	https://doi.org/10.1016/j.jalz.2019.01.015
Publication status	Published - Jun 2019

Keywords

Alzheimer
Amyloid
CSF
Inflammation
Neurofilaments
Tau
YKL-40

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10.1016/j.jalz.2019.01.015

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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 & dementia : the journal of the Alzheimer's Association, 15(6), 742-753. https://doi.org/10.1016/j.jalz.2019.01.015

Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study. / Lleó, Alberto; Alcolea, Daniel; Martínez-Lage, Pablo et al.
In: Alzheimer's & dementia : the journal of the Alzheimer's Association, Vol. 15, No. 6, 06.2019, p. 742-753.

Research output: Contribution to journal › Journal article › Research › peer-review

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 & dementia : the journal of the Alzheimer's Association, vol. 15, no. 6, pp. 742-753. https://doi.org/10.1016/j.jalz.2019.01.015

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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",

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

language = "English",

volume = "15",

pages = "742--753",

journal = "Alzheimer's \& dementia : the journal of the Alzheimer's Association",

issn = "1552-5260",

publisher = "Elsevier Inc",

number = "6",

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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

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 (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

U2 - 10.1016/j.jalz.2019.01.015

DO - 10.1016/j.jalz.2019.01.015

M3 - Journal article

C2 - 30967340

SN - 1552-5260

VL - 15

SP - 742

EP - 753

JO - Alzheimer's & dementia : the journal of the Alzheimer's Association

JF - Alzheimer's & dementia : the journal of the Alzheimer's Association

IS - 6

ER -

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

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Keywords

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