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Glutaminyl cyclase activity correlates with levels of Aβ peptides and mediators of angiogenesis in cerebrospinal fluid of Alzheimer’s disease patients

التفاصيل البيبلوغرافية
العنوان: Glutaminyl cyclase activity correlates with levels of Aβ peptides and mediators of angiogenesis in cerebrospinal fluid of Alzheimer’s disease patients
المؤلفون: Sisi Durieux, Antje Meyer, Philip Scheltens, Claire Bridel, Inge Lues, Marleen J. A. Koel-Simmelink, Matthias Orth, Charlotte E. Teunissen, Torsten Hoffmann
المساهمون: Clinical chemistry, Neurology, Amsterdam Neuroscience - Neurodegeneration
المصدر: Alzheimer's Research & Therapy
Alzheimer's Research and Therapy, 9(1):38. BioMed Central
Bridel, C, Hoffmann, T, Meyer, A, Durieux, S, Koel-Simmelink, M A, Orth, M, Scheltens, P, Lues, I & Teunissen, C E 2017, ' Glutaminyl cyclase activity correlates with levels of Aβ peptides and mediators of angiogenesis in cerebrospinal fluid of Alzheimer’s disease patients ', Alzheimer's Research and Therapy, vol. 9, no. 1, 38 . https://doi.org/10.1186/s13195-017-0266-6
Alzheimer’s Research & Therapy, Vol 9, Iss 1, Pp 1-10 (2017)
بيانات النشر: BioMed Central, 2017.
سنة النشر: 2017
مصطلحات موضوعية: 0301 basic medicine, Apolipoprotein E, Male, Neurology, Angiogenesis, Statistics as Topic, lcsh:RC346-429, 0302 clinical medicine, Cerebrospinal fluid, Angiogenic Proteins, Aged, 80 and over, biology, Angiogenesis Modulating Agents, Middle Aged, Glutaminyl cyclase, Aminoacyltransferases, Angiopoietin receptor, Disease Progression, Biomarker (medicine), Female, Alzheimer’s disease, medicine.medical_specialty, Amyloid beta, Cognitive Neuroscience, Sensitivity and Specificity, lcsh:RC321-571, 03 medical and health sciences, Alzheimer Disease, Internal medicine, medicine, 3pE-Aβ42, Humans, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Aged, Amyloid beta-Peptides, business.industry, Research, Reproducibility of Results, Enzyme Activation, 030104 developmental biology, Endocrinology, Pharmacodynamics, biology.protein, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers
الوصف: 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 0.5, p 0.35, p =
اللغة: English
تدمد: 1758-9193
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::98cc20bfd89d74b71fb2dfc6581aa84d
http://europepmc.org/articles/PMC5461753
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....98cc20bfd89d74b71fb2dfc6581aa84d
قاعدة البيانات: OpenAIRE
الوصف
تدمد:17589193