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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Karger Publishers
2016-07-01
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| Series: | Dementia and Geriatric Cognitive Disorders Extra |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/447239 |
| _version_ | 1819090666884431872 |
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| author | Annika Öhrfelt Per Johansson Anders Wallin Ulf Andreasson Henrik Zetterberg Kaj Blennow Johan Svensson |
| author_facet | Annika Öhrfelt Per Johansson Anders Wallin Ulf Andreasson Henrik Zetterberg Kaj Blennow Johan Svensson |
| author_sort | Annika Öhrfelt |
| collection | DOAJ |
| 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-tau231) 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-tau231 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. |
| first_indexed | 2024-12-21T22:27:28Z |
| format | Article |
| id | doaj.art-d809d4716be4416883043fa7ece91d06 |
| institution | Directory Open Access Journal |
| issn | 1664-5464 |
| language | English |
| last_indexed | 2024-12-21T22:27:28Z |
| publishDate | 2016-07-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Dementia and Geriatric Cognitive Disorders Extra |
| spelling | doaj.art-d809d4716be4416883043fa7ece91d062022-12-21T18:48:11ZengKarger PublishersDementia and Geriatric Cognitive Disorders Extra1664-54642016-07-016228329410.1159/000447239447239Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1 in Patients with Alzheimer's DiseaseAnnika ÖhrfeltPer JohanssonAnders WallinUlf AndreassonHenrik ZetterbergKaj BlennowJohan SvenssonBackground: 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-tau231) 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-tau231 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.http://www.karger.com/Article/FullText/447239Alzheimer’s diseaseBiomarkersCerebrospinal fluidDJ-1Neuron-specific enolaseUbiquitin carboxyl-terminal hydrolase L1Tau phosphorylated at threonine 231 |
| spellingShingle | Annika Öhrfelt Per Johansson Anders Wallin Ulf Andreasson Henrik Zetterberg Kaj Blennow Johan Svensson Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1 in Patients with Alzheimer's Disease Dementia and Geriatric Cognitive Disorders Extra Alzheimer’s disease Biomarkers Cerebrospinal fluid DJ-1 Neuron-specific enolase Ubiquitin carboxyl-terminal hydrolase L1 Tau phosphorylated at threonine 231 |
| 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 | Alzheimer’s disease Biomarkers Cerebrospinal fluid DJ-1 Neuron-specific enolase Ubiquitin carboxyl-terminal hydrolase L1 Tau phosphorylated at threonine 231 |
| url | http://www.karger.com/Article/FullText/447239 |
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