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

Öhrfelt, Annika; Johansson, Per LU ; Wallin, Anders; Andreasson, Ulf; Zetterberg, Henrik; Blennow, Kaj and Svensson, Johan (2016) In Dementia and Geriatric Cognitive Disorders Extra 6(2). p.94-283
Abstract

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 =... (More)

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.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Journal Article
in
Dementia and Geriatric Cognitive Disorders Extra
volume
6
issue
2
pages
12 pages
publisher
Karger
external identifiers
  • Scopus:84978972848
ISSN
1664-5464
DOI
10.1159/000447239
language
English
LU publication?
no
id
8dc8a8c7-7ebf-45f8-bcf1-7ed99c5f49be
date added to LUP
2016-09-29 16:20:52
date last changed
2017-01-01 08:35:33
@article{8dc8a8c7-7ebf-45f8-bcf1-7ed99c5f49be,
  abstract     = {<p>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).</p><p>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).</p><p>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.</p><p>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.</p>},
  author       = {Öhrfelt, Annika and Johansson, Per and Wallin, Anders and Andreasson, Ulf and Zetterberg, Henrik and Blennow, Kaj and Svensson, Johan},
  issn         = {1664-5464},
  keyword      = {Journal Article},
  language     = {eng},
  month        = {08},
  number       = {2},
  pages        = {94--283},
  publisher    = {Karger},
  series       = {Dementia and Geriatric Cognitive Disorders Extra},
  title        = {Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1 in Patients with Alzheimer's Disease},
  url          = {http://dx.doi.org/10.1159/000447239},
  volume       = {6},
  year         = {2016},
}