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Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1 in Patients with Alzheimer's Disease

BACKGROUND: Dysfunctions of the ubiquitin proteasome system (UPS), including the highly abundant neuronal enzyme ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and autophagy-related changes (lysosomal degradation) are implicated in several neurodegenerative disorders including Alzheimer's d...

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Autores principales: Öhrfelt, Annika, Johansson, Per, Wallin, Anders, Andreasson, Ulf, Zetterberg, Henrik, Blennow, Kaj, Svensson, Johan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: S. Karger AG 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965532/
https://www.ncbi.nlm.nih.gov/pubmed/27504117
http://dx.doi.org/10.1159/000447239
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author Öhrfelt, Annika
Johansson, Per
Wallin, Anders
Andreasson, Ulf
Zetterberg, Henrik
Blennow, Kaj
Svensson, Johan
author_facet Öhrfelt, Annika
Johansson, Per
Wallin, Anders
Andreasson, Ulf
Zetterberg, Henrik
Blennow, Kaj
Svensson, Johan
author_sort Öhrfelt, Annika
collection PubMed
description BACKGROUND: Dysfunctions of the ubiquitin proteasome system (UPS), including the highly abundant neuronal enzyme ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and autophagy-related changes (lysosomal degradation) are implicated in several neurodegenerative disorders including Alzheimer's disease (AD). METHOD: This study evaluated cerebrospinal fluid (CSF) levels of UCH-L1, protein deglycase (DJ-1), neuron-specific enolase (NSE), and tau phosphorylated at threonine 231 (P-tau(231)) in two independent patient and control cohorts. Cohort 1 included CSF samples from subjects having an AD biomarker profile (n = 10) or a control biomarker profile (n = 31), while cohort 2 was a monocenter clinical study including patients with AD (n = 32), mild cognitive impairment (n = 13), other dementias (n = 15), as well as cognitively healthy controls (n = 20). RESULTS: UCH-L1 and P-tau(231) were elevated in AD patients compared to controls in both cohorts. CSF levels of DJ-1 and NSE were unchanged in the AD group, whereas they were decreased in the group of other dementia compared to controls in the clinical study. CONCLUSION: Our main findings support that the UPS pathway may be impaired in AD, and UCH-L1 may serve as an additional CSF biomarker for AD.
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spelling pubmed-49655322016-08-08 Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1 in Patients with Alzheimer's Disease Öhrfelt, Annika Johansson, Per Wallin, Anders Andreasson, Ulf Zetterberg, Henrik Blennow, Kaj Svensson, Johan Dement Geriatr Cogn Dis Extra Original Research Article BACKGROUND: Dysfunctions of the ubiquitin proteasome system (UPS), including the highly abundant neuronal enzyme ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and autophagy-related changes (lysosomal degradation) are implicated in several neurodegenerative disorders including Alzheimer's disease (AD). METHOD: This study evaluated cerebrospinal fluid (CSF) levels of UCH-L1, protein deglycase (DJ-1), neuron-specific enolase (NSE), and tau phosphorylated at threonine 231 (P-tau(231)) in two independent patient and control cohorts. Cohort 1 included CSF samples from subjects having an AD biomarker profile (n = 10) or a control biomarker profile (n = 31), while cohort 2 was a monocenter clinical study including patients with AD (n = 32), mild cognitive impairment (n = 13), other dementias (n = 15), as well as cognitively healthy controls (n = 20). RESULTS: UCH-L1 and P-tau(231) were elevated in AD patients compared to controls in both cohorts. CSF levels of DJ-1 and NSE were unchanged in the AD group, whereas they were decreased in the group of other dementia compared to controls in the clinical study. CONCLUSION: Our main findings support that the UPS pathway may be impaired in AD, and UCH-L1 may serve as an additional CSF biomarker for AD. S. Karger AG 2016-07-15 /pmc/articles/PMC4965532/ /pubmed/27504117 http://dx.doi.org/10.1159/000447239 Text en Copyright © 2016 by S. Karger AG, Basel http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.
spellingShingle Original Research Article
Öhrfelt, Annika
Johansson, Per
Wallin, Anders
Andreasson, Ulf
Zetterberg, Henrik
Blennow, Kaj
Svensson, Johan
Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1 in Patients with Alzheimer's Disease
title Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1 in Patients with Alzheimer's Disease
title_full Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1 in Patients with Alzheimer's Disease
title_fullStr Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1 in Patients with Alzheimer's Disease
title_full_unstemmed Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1 in Patients with Alzheimer's Disease
title_short Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1 in Patients with Alzheimer's Disease
title_sort increased cerebrospinal fluid levels of ubiquitin carboxyl-terminal hydrolase l1 in patients with alzheimer's disease
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965532/
https://www.ncbi.nlm.nih.gov/pubmed/27504117
http://dx.doi.org/10.1159/000447239
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