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

2019; Wiley; Volume: 15; Issue: 6 Linguagem: Inglês

10.1016/j.jalz.2019.01.015

1552-5279

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

Neurological Disease Mechanisms and Treatments

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.