Cerebrospinal fluid levels of the neurotrophic factor neuroleukin are increased in early Alzheimer’s disease, but not in cerebral amyloid angiopathy

Abstract

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.

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Proximity extension assay in cerebrospinal fluid identifies neurofilament light chain as biomarker of neurodegeneration in sporadic cerebral amyloid angiopathy

“…Most of the sCAA patients (n = 42) were enrolled through cross-sectional cohort studies (Cerebral Amyloid Angiopathy Vascular Imaging and fluid markers of Amyloid deposition (CAVIA), BIOmarkers for cogNitive Impairment due to Cerebral amyloid angiopathy (BIONIC), aimed at identifying new CSF biomarkers for sCAA at the RUMC (Website: www.radboudumc. nl/BCS) [9][10][11][12][13]. The two remaining sCAA patients were identified through routine diagnostic workflow at the hospital.…”

Correction to: Cerebrospinal fluid levels of the neurotrophic factor neuroleukin are increased in early Alzheimer’s disease, but not in cerebral amyloid angiopathy

“…Following the publication of the original article [ 1 ] the authors noticed that the published Fig. 2 is incorrect.…”

“…The authors uploaded the incorrect figure during the proofing process. The original article [ 1 ] has been updated. The correct Fig.…”