Gunn, AP, Wong, BX, McLean, C et al. (4 more authors) (2021) Increased glutaminyl cyclase activity in brains of Alzheimer’s disease individuals. Journal of Neurochemistry, 156 (6). pp. 979-987. ISSN 0022-3042
Abstract
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 (AIBL) 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Alzheimer’s Disease; Amyloid‐β; Glutaminyl Cyclase; Monocyte; Pyroglutamate |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 17 Jul 2020 09:23 |
Last Modified: | 21 Apr 2023 15:05 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1111/jnc.15114 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:163281 |