Cerebrospinal fluid levels of the neurotrophic factor neuroleukin are increased in early Alzheimer's disease, but not in cerebral amyloid angiopathy
De Kort, A.M. (Department of Neurology. Radboud University Medical Center. Donders Institute for Brain. Cognition and Behaviour. Radboud Alzheimer Centre)
Kuiperij, H.B. (Department of Neurology. Radboud University Medical Center. Donders Institute for Brain. Cognition and Behaviour. Radboud Alzheimer Centre)
Alcolea, Daniel (Institut d'Investigació Biomèdica Sant Pau)
Kersten, I. (Department of Neurology. Radboud University Medical Center. Donders Institute for Brain. Cognition and Behaviour. Radboud Alzheimer Centre)
Versleijen, A.A.M. (Department of Laboratory Medicine. Radboud University Medical Center)
Greenberg, S.M. (Massachusetts General Hospital (Boston))
Stoops, E. (ADx NeuroSciences)
Schreuder, F.H.B.M. (Department of Neurology. Radboud University Medical Center. Donders Institute for Brain. Cognition and Behaviour. Radboud Alzheimer Centre)
Klijn, C.J.M. (Department of Neurology. Radboud University Medical Center. Donders Institute for Brain. Cognition and Behaviour. Radboud Alzheimer Centre)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Claassen, Jurgen A. H. R (Radboud University Medical Centre. Department of Geriatrics)
Verbeek, M.M. (Department of Laboratory Medicine. Radboud University Medical Center)
Universitat Autònoma de Barcelona

Fecha:	2021
Resumen:	Background: Neuroleukin (NLK) is a protein with neurotrophic properties and is present in a proportion of senile plaques and amyloid laden vessels. It has been suggested that NLK is part of a neuroprotective response to amyloid β-induced cell death. The aim of our study was to investigate the value of cerebrospinal fluid (CSF) NLK levels as a biomarker of vascular amyloid deposition in patients with cerebral amyloid angiopathy (CAA) and in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). Methods: CSF NLK levels were quantified by ELISA in CAA patients (n = 25) and controls (n = 27) and in two independent samples of aMCI patients, AD patients, and controls: (1) From the Radboud University Medical Center (Nijmegen), we included n = 19 aMCI patients, n = 40 AD patients, and n = 32 controls. (2) From the Hospital of Sant Pau (Barcelona), we included n = 33 aMCI patients, n = 17 AD patients, and n = 50 controls. Results: CSF NLK levels were similar in CAA patients and controls (p = 0. 95). However, we found an elevated CSF concentration of NLK in aMCI (p < 0. 0001) and AD patients (p < 0. 0001) compared to controls in both samples sets. In addition, we found a correlation of CSF NLK with CSF YKL-40 (age-adjusted-spearman-rank-coefficient = 0. 82, p < 0. 0001) in aMCI/AD patients, a well-known glial marker of neuro-inflammation. Conclusions: We found that CSF NLK levels are elevated in aMCI and AD patients compared to controls, but are not increased in CAA patients. CSF NLK levels may be related to an increased neuroinflammatory state in early stages of AD, given its association with YKL-40.
Nota:	Altres ajuts: BIONIC project (no. 733050822); "Memorabel," the research and innovation program for dementia, as part of the Dutch national "Deltaplan for Dementia"; the National Institutes of Health, USA (5R01NS104147-02); Dutch Heart Foundation (grant 2012 T077); ASPASIA grant from The Netherlands Organization for Health Research and Development, ZonMW (grant 015008048); senior clinical scientist grant of the Dutch Heart Foundation (grant 2019 T060); CIBERNED; Instituto de Salud Carlos III; Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, "Una manera de hacer Europa"; Generalitat de Catalunya; Fundació "La Marató TV3"; Fundació Bancària Obra Social La Caixa; Fundación BBVA; Fundación Española para el Fomento de la Investigación de la Esclerosis Lateral Amiotrófica (FUNDELA); Global Brain Health Institute; Fundació Catalana Síndrome de Down; Fundació Víctor Grífols i Lucas.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Cerebrospinal fluid ; Biomarkers ; Alzheimer's disease ; Amyloid ; Cerebral amyloid angiopathy ; Neuroleukin ; Neuro-inflammation
Publicado en:	Alzheimer's research & therapy, Vol. 13 Núm. 1 (december 2021) , p. 160, ISSN 1758-9193

DOI: 10.1186/s13195-021-00899-0
PMID: 34560885

10 p, 855.6 KB

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