Cerebrospinal fluid levels of the neurotrophic factor neuroleukin are increased in early Alzheimer's disease, but not in cerebral amyloid angiopathy
Por:
De Kort, AM, Kuiperij, HB, Alcolea, D, Kersten, I, Versleijen, AAM, Greenberg, SM, Stoops, E, Schreuder, FHBM, Klijn, CJM, Lleo, A, Claassen, JAHR, Verbeek, MM
Publicada:
24 sep 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 beta-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.
Filiaciones:
De Kort, AM:
Radboud Univ Nijmegen Med Ctr, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, POB 9101, NL-6500 HB Nijmegen, Netherlands
Kuiperij, HB:
Radboud Univ Nijmegen Med Ctr, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, POB 9101, NL-6500 HB Nijmegen, Netherlands
Alcolea, D:
Univ Autonoma Barcelona, Dept Neurol, St Pau Memory Unit, Hosp Santa Creu & St Pau,Biomed Res Inst St Pau, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Kersten, I:
Radboud Univ Nijmegen Med Ctr, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, POB 9101, NL-6500 HB Nijmegen, Netherlands
Versleijen, AAM:
Radboud Univ Nijmegen Med Ctr, Dept Lab Med, Nijmegen, Netherlands
Greenberg, SM:
Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA
Stoops, E:
ADx NeuroSci, Ghent, Belgium
Schreuder, FHBM:
Radboud Univ Nijmegen Med Ctr, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, POB 9101, NL-6500 HB Nijmegen, Netherlands
Klijn, CJM:
Radboud Univ Nijmegen Med Ctr, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, POB 9101, NL-6500 HB Nijmegen, Netherlands
Lleo, A:
Univ Autonoma Barcelona, Dept Neurol, St Pau Memory Unit, Hosp Santa Creu & St Pau,Biomed Res Inst St Pau, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Claassen, JAHR:
Radboud Univ Nijmegen Med Ctr, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav, Dept Geriatr, Nijmegen, Netherlands
Verbeek, MM:
Radboud Univ Nijmegen Med Ctr, Radboud Alzheimer Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, POB 9101, NL-6500 HB Nijmegen, Netherlands
Radboud Univ Nijmegen Med Ctr, Dept Lab Med, Nijmegen, Netherlands
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