Glutaminyl cyclase activity correlates with levels of ABeta peptides and mediators of angiogenesis in cerebrospinal fluid of Alzheimers disease patients

Background Pyroglutamylation of truncated Aβ peptides, which is catalysed by enzyme glutaminyl cyclase (QC), generates pE-Aβ species with enhanced aggregation propensities and resistance to most amino-peptidases and endo-peptidases. pE-Aβ species have been identified as major constituents of Aβ plaq...

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Bibliographic Details
Published in:Alzheimer's research & therapy 2017-01, Vol.9
Main Authors: Bridel, Claire, Hoffmann, Torsten, Meyer, Antje, Durieux, Sisi, Koel-Simmelink, Marleen A, Orth, Matthias, Scheltens, Philip, Lues, Inge, Teunissen, Charlotte E
Format: Article
Language:English
Subjects:
Aging
Alzheimer's disease
Amino acids
Angiogenesis
Biomarkers
Cerebrospinal fluid
Cognitive ability
Dementia
Enzymes
Immunoassay
Inflammation
Laboratories
Memory
Neurodegeneration
Peptides
Vascular endothelial growth factor
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Summary:Background Pyroglutamylation of truncated Aβ peptides, which is catalysed by enzyme glutaminyl cyclase (QC), generates pE-Aβ species with enhanced aggregation propensities and resistance to most amino-peptidases and endo-peptidases. pE-Aβ species have been identified as major constituents of Aβ plaques and reduction of pE-Aβ species is associated with improvement of cognitive tasks in animal models of Alzheimer’s disease (AD). Pharmacological inhibition of QC has thus emerged as a promising therapeutic approach for AD. Here, we question whether cerebrospinal fluid (CSF) QC enzymatic activity differs between AD patients and controls and whether inflammatory or angiogenesis mediators, some of which are potential QC substrates, and/or Aβ peptides may serve as pharmacodynamic read-outs for QC inhibition. Methods QC activity, Aβ peptides and inflammatory or angiogenesis mediators were measured in CSF of a clinically well-characterized cohort of 20 mild AD patients, 20 moderate AD patients and 20 subjective memory complaints (SMC) controls. Correlation of these parameters with core diagnostic CSF AD biomarkers (Aβ42, tau and p-tau) and clinical features was evaluated. Results QC activity shows a tendency to decrease with AD progression (p = 0.129). The addition of QC activity to biomarkers tau and p-tau significantly increases diagnostic power (ROC-AUCTAU = 0.878, ROC-AUCTAU&QC = 0.939 and ROC-AUCpTAU = 0.820, ROC-AUCpTAU&QC = 0.948). In AD and controls, QC activity correlates with Aβ38 (r = 0.83, p 
ISSN:1758-9193
DOI:10.1186/s13195-017-0266-6