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

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Author

  • Annika Öhrfelt
  • Per Johansson
  • Anders Wallin
  • Ulf Andreasson
  • Henrik Zetterberg
  • Kaj Blennow
  • Johan Svensson

Summary, in English

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.

Publishing year

2016-08-10

Language

English

Pages

94-283

Publication/Series

Dementia and Geriatric Cognitive Disorders Extra

Volume

6

Issue

2

Document type

Journal article

Publisher

Karger

Keywords

  • Journal Article

Status

Published

Project

  • Endocrine and diagnostic aspects of cognitive impairment

ISBN/ISSN/Other

  • ISSN: 1664-5464