Increased glutaminyl cyclase activity in brains of Alzheimer's disease individuals.
Alzheimer's disease
amyloid-β
glutaminyl cyclase
monocyte
pyroglutamate
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
revised:
27
05
2020
received:
09
03
2020
accepted:
24
06
2020
pubmed:
3
7
2020
medline:
22
6
2021
entrez:
3
7
2020
Statut:
ppublish
Résumé
Glutaminyl cyclases (QC) catalyze the formation of neurotoxic pGlu-modified amyloid-β peptides found in the brains of people with Alzheimer's disease (AD). Reports of several-fold increases in soluble QC (sQC) expression in the brain and peripheral circulation of AD individuals has prompted the development of QC inhibitors as potential AD therapeutics. There is, however, a lack of standardized quantitative data on QC expression in human tissues, precluding inter-laboratory comparison and validation. We tested the hypothesis that QC is elevated in AD tissues by quantifying levels of sQC protein and activity in post-mortem brain tissues from AD and age-matched control individuals. We found a modest but statistically significant increase in sQC protein, which paralleled a similar increase in enzyme activity. In plasma samples sourced from the Australian Imaging, Biomarker and Lifestyle study we determined that QC activity was not different between the AD and control group, though a modest increase was observed in female AD individuals compared to controls. Plasma QC activity was further correlated with levels of circulating monocytes in AD individuals. These data provide quantitative evidence that alterations in QC expression are associated with AD pathology.
Substances chimiques
Biomarkers
0
Enzyme Inhibitors
0
Aminoacyltransferases
EC 2.3.2.-
glutaminyl-peptide cyclotransferase
EC 2.3.2.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
979-987Informations de copyright
© 2020 International Society for Neurochemistry.
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