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

Research output: Contribution to journalArticleAcademicpeer-review

81 Citations (Scopus)


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 languageEnglish
Pages (from-to)742-753
Number of pages12
JournalAlzheimer's and Dementia
Issue number6
Publication statusPublished - 1 Jun 2019


  • Alzheimer
  • Amyloid
  • CSF
  • Inflammation
  • Neurofilaments
  • Tau
  • YKL-40

Cite this