Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) S18Y polymorphism in Alzheimer's disease

Madeleine Zetterberg,Henrik Zetterberg,Kaj Blennow,Annica Sjölander,Lennart Minthon,Mona Palmér,Niels Andreasen,Anders Wallin,Malin Von Otter,Sara Landgren

doi:10.1186/1750-1326-5-11

Abstract

Alzheimer's disease (AD) is characterized by protein aggregates, i.e. senile plaques and neurofibrillary tangles. The ubiquitin-proteasome system has been proposed a role in proteolytic removal of these protein aggregates. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a de-ubiquitinating enzyme with important functions in recycling of ubiquitin. The S18Y polymorphism of the UCHL1 gene confers protection against Parkinson's disease. In this study, the genotype and allele frequencies of the UCHL1 S18Y polymorphism were investigated in 452 AD patients and 234 control subjects, recruited from four memory clinics in Sweden. Using a binary logistic regression model including UCHL1 allele A and APOE ε4 allele positivity, age and sex as covariates with AD diagnosis as dependent variable, an adjusted OR of 0.82 ([95% CI 0.55-1.24], P = 0.35) was obtained for a positive UCHL1 allele A carrier status. The present study thus do not support a protective effect of the UCHL1 S18Y polymorphism against AD.

Highlights

Alzheimer’s disease (AD) is characterized by protein aggregates, i.e. senile plaques and neurofibrillary tangles
Proteins destined for degradation by the ubiquitin-proteasome system (UPS) are labelled with a 76-amino acid peptide, ubiquitin, through a series of conjugation steps by the E1, E2 and E3 enzymes respectively
Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) has an important role in recycling of ubiquitin through hydrolysis of peptide-ubiquitin bonds and processing of ubiquitin precursors, but it possesses ubiquitin ligase activity [7]

Summary

Introduction

Alzheimer’s disease (AD) is characterized by protein aggregates, i.e. senile plaques and neurofibrillary tangles. The purpose of this study was to investigate the UCHL1 S18Y polymorphism in AD patients and controls in the Swedish population. For subsets of the participants, have previously collected data on levels of CSF biochemical markers and neuropathological scores for AD, associations between the UCHL1 S18Y polymorphism and these variables could be investigated in addition to the genetic risk analysis.

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