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

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

doi:10.1159/000447239

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

Dement Geriatr Cogn Dis Extra. 2016 Jul 15;6(2):283-94. doi: 10.1159/000447239. eCollection 2016 May-Aug.

Authors

Annika Öhrfelt¹, Per Johansson², Anders Wallin¹, Ulf Andreasson¹, Henrik Zetterberg³, Kaj Blennow¹, Johan Svensson⁴

Affiliations

¹ Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital Mölndal, Sahlgrenska Academy, University of Gothenburg, Mölndal, Gothenburg, Sweden.
² Department of Neuropsychiatry, Skaraborg Hospital, Falköping, Gothenburg, Sweden; Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³ Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital Mölndal, Sahlgrenska Academy, University of Gothenburg, Mölndal, Gothenburg, Sweden; UCL Institute of Neurology, London, UK.
⁴ Department of Endocrinology, Skaraborg Hospital, Skövde, Gothenburg, Sweden; Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

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 = 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.

Keywords: Alzheimer's disease; Biomarkers; Cerebrospinal fluid; DJ-1; Neuron-specific enolase; Tau phosphorylated at threonine 231; Ubiquitin carboxyl-terminal hydrolase L1.