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[O3–10–03]: LONGITUDINAL CEREBROSPINAL FLUID BIOMARKER TRAJECTORIES ALONG THE ALZHEIMER'S DISEASE CONTINUUM: A MULTICENTRE EUROPEAN STUDY

2017; Wiley; Volume: 13; Issue: 7S_Part_19 Linguagem: Inglês

10.1016/j.jalz.2017.07.359

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, Andrea Izagirre, Babette L.R. Reijs, Lucia Farotti, Juan Fortea, Lutz Frölich, Isabel Santana, José Luís Molinuevo, Silvain Lehmann, Pieter Jelle Visser, Charlotte E. Teunissen, Henrik Zetterberg, Kaj Blennow,

Dementia and Cognitive Impairment Research

Our aim was to characterize the within-person trajectories of cerebrospinal fluid (CSF) biomarkers along the Alzheimer's disease (AD) continuum. We included 407 subjects from the multicenter BIOMARKAPD project from whom at least two CSF samples were obtained. Baseline diagnosis were: healthy controls (HC=146), subjective cognitive decline (SCD=71), mild cognitive impairment (MCI=101), and AD dementia (AD=89). We measured baseline and follow-up CSF levels of amyloid-β (Aβ)1–42, Aβ1–40, Aβ1–38, total tau (t-tau), phosphorylated tau (p-tau), YKL-40 and neurofilament-light (NfL). Analytes were determined in a central laboratory (Gothenburg) using commercial assays (MSD: Aβ1–42, Aβ1–40, Aβ1–38; Fujirebio-Europe: t-tau and p-tau; R&D: YKL-40 and UmanDiagnostics: NfL). We compared baseline CSF biomarkers between groups using ANCOVA (adjusted by age, sex and APOEε4 status), and compared longitudinal changes using generalized linear mixed models with subject-specific random intercepts and random time slopes. Time from study entry, diagnosis, APOEε4 status and their interactions together with gender and baseline age were included as fixed-effects. We analyzed 847 CSF samples from 407 subjects. Median time between samples was 2.4 years (range 0.4–6.2). In the adjusted baseline cross-sectional analysis, the AD group had higher levels of t-tau, p-tau, YKL-40 and NfL and lower levels of Aβ1–42 compared to HC, SCD and MCI (ANCOVA, p<0.05). There were no differences in Aβ1–40 or Aβ1–38 between groups. There was a significant association between age and all biomarkers. Males had higher NfL levels than females. In the longitudinal analysis, t-tau, p-tau, YKL-40, Aβ1–38, Aβ1–40 and Aβ1–42 had a positive within-person adjusted annual rate of change. The rate of change of YKL-40 was higher in MCI and AD and the rate of change of NfL was higher in MCI. The slopes of t-tau, p-tau, YKL-40 and NfL were more pronounced in APOE ε4 subjects. Our findings suggest that CSF biomarker levels are dynamic and tend to increase with age. The rates of change of core AD biomarkers (Aβ1–42, t-tau and p-tau) are modified by the APOE ε4 status and vary in different stages of the AD continuum. These facts should be taken into account in longitudinal observational studies and in clinical trials that use CSF as an endpoint.