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Open Access 01-12-2010 | Short report

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

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

Published in: Molecular Neurodegeneration | Issue 1/2010

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.

Oddo S: The ubiquitin-proteasome system in Alzheimer's disease. J Cell Mol Med. 2008, 12: 363-373. 10.1111/j.1582-4934.2008.00276.x.PubMedPubMedCentralCrossRef

Petroski MD: The ubiquitin system, disease, and drug discovery. BMC Biochem. 2008, 9 (Suppl 1): S7-10.1186/1471-2091-9-S1-S7.PubMedPubMedCentralCrossRef

Tai HC, Schuman EM: Ubiquitin, the proteasome and protein degradation in neuronal function and dysfunction. Nat Rev Neurosci. 2008, 9: 826-838. 10.1038/nrn2499.PubMedCrossRef

Dhillon AP, Rode J, Dhillon DP, Moss E, Thompson RJ, Spiro SG, Corrin B: Neural markers in carcinoma of the lung. Br J Cancer. 1985, 51: 645-652.PubMedPubMedCentralCrossRef

Otsuki T, Yata K, Takata-Tomokuni A, Hyodoh F, Miura Y, Sakaguchi H, Hatayama T, Hatada S, Tsujioka T, Sato Y, Murakami H, Sadahira Y, Sugihara T: Expression of protein gene product 9.5 (PGP9.5)/ubiquitin-C-terminal hydrolase 1 (UCHL-1) in human myeloma cells. Br J Haematol. 2004, 127: 292-298. 10.1111/j.1365-2141.2004.05205.x.PubMedCrossRef

Thompson RJ, Doran JF, Jackson P, Dhillon AP, Rode J: PGP 9.5--a new marker for vertebrate neurons and neuroendocrine cells. Brain Res. 1983, 278: 224-228. 10.1016/0006-8993(83)90241-X.PubMedCrossRef

Healy DG, Abou-Sleiman PM, Wood NW: Genetic causes of Parkinson's disease: UCHL-1. Cell Tissue Res. 2004, 318: 189-194. 10.1007/s00441-004-0917-3.PubMedCrossRef

Osaka H, Wang YL, Takada K, Takizawa S, Setsuie R, Li H, Sato Y, Nishikawa K, Sun YJ, Sakurai M, Harada T, Hara Y, Kimura I, Chiba S, Namikawa K, Kiyama H, Noda M, Aoki S, Wada K: Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron. Hum Mol Genet. 2003, 12: 1945-1958. 10.1093/hmg/ddg211.PubMedCrossRef

Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, Harta G, Brownstein MJ, Jonnalagada S, Chernova T, Dehejia A, Lavedan C, Gasser T, Steinbach PJ, Wilkinson KD, Polymeropoulos MH: The ubiquitin pathway in Parkinson's disease. Nature. 1998, 395: 451-452. 10.1038/26652.PubMedCrossRef

10.

Setsuie R, Wada K: The functions of UCH-L1 and its relation to neurodegenerative diseases. Neurochem Int. 2007, 51: 105-111. 10.1016/j.neuint.2007.05.007.PubMedCrossRef

11.

Liu Y, Fallon L, Lashuel HA, Liu Z, Lansbury PT: The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility. Cell. 2002, 111: 209-218. 10.1016/S0092-8674(02)01012-7.PubMedCrossRef

12.

Kyratzi E, Pavlaki M, Stefanis L: The S18Y polymorphic variant of UCH-L1 confers an antioxidant function to neuronal cells. Hum Mol Genet. 2008, 17: 2160-2171. 10.1093/hmg/ddn115.PubMedCrossRef

13.

Carmine Belin A, Westerlund M, Bergman O, Nissbrandt H, Lind C, Sydow O, Galter D: S18Y in ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) associated with decreased risk of Parkinson's disease in Sweden. Parkinsonism Relat Disord. 2007, 13: 295-298. 10.1016/j.parkreldis.2006.12.002.PubMedCrossRef

14.

Elbaz A, Levecque C, Clavel J, Vidal JS, Richard F, Correze JR, Delemotte B, Amouyel P, Alperovitch A, Chartier-Harlin MC, Tzourio C: S18Y polymorphism in the UCH-L1 gene and Parkinson's disease: evidence for an age-dependent relationship. Mov Disord. 2003, 18: 130-137. 10.1002/mds.10326.PubMedCrossRef

15.

Maraganore DM, Farrer MJ, Hardy JA, Lincoln SJ, McDonnell SK, Rocca WA: Case-control study of the ubiquitin carboxy-terminal hydrolase L1 gene in Parkinson's disease. Neurology. 1999, 53: 1858-1860.PubMedCrossRef

16.

Maraganore DM, Lesnick TG, Elbaz A, Chartier-Harlin MC, Gasser T, Kruger R, Hattori N, Mellick GD, Quattrone A, Satoh J, Toda T, Wang J, Ioannidis JP, de Andrade M, Rocca WA: UCHL1 is a Parkinson's disease susceptibility gene. Ann Neurol. 2004, 55: 512-521. 10.1002/ana.20017.PubMedCrossRef

17.

Hutter CM, Samii A, Factor SA, Nutt JG, Higgins DS, Bird TD, Griffith A, Roberts JW, Leis BC, Montimurro JS, Kay DM, Edwards KL, Payami H, Zabetian CP: Lack of evidence for an association between UCHL1 S18Y and Parkinson's disease. Eur J Neurol. 2008, 15: 134-139.PubMedPubMedCentralCrossRef

18.

Forero DA, Benitez B, Arboleda G, Yunis JJ, Pardo R, Arboleda H: Analysis of functional polymorphisms in three synaptic plasticity-related genes (BDNF, COMT AND UCHL1) in Alzheimer's disease in Colombia. Neurosci Res. 2006, 55: 334-341. 10.1016/j.neures.2006.04.006.PubMedCrossRef

19.

Xue S, Jia J: Genetic association between Ubiquitin Carboxy-terminal Hydrolase-L1 gene S18Y polymorphism and sporadic Alzheimer's disease in a Chinese Han population. Brain Res. 2006, 1087: 28-32. 10.1016/j.brainres.2006.02.121.PubMedCrossRef

20.

Andersson ME, Sjolander A, Andreasen N, Minthon L, Hansson O, Bogdanovic N, Jern C, Jood K, Wallin A, Blennow K, Zetterberg H: Kinesin gene variability may affect tau phosphorylation in early Alzheimer's disease. Int J Mol Med. 2007, 20: 233-239.PubMed

21.

Zetterberg M, Landgren S, Andersson ME, Palmer MS, Gustafson DR, Skoog I, Minthon L, Thelle DS, Wallin A, Bogdanovic N, Andreasen N, Blennow K, Zetterberg H: Association of complement factor H Y402H gene polymorphism with Alzheimer's disease. Am J Med Genet B Neuropsychiatr Genet. 2007, 147B (6): 720-6.CrossRef

22.

McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984, 34: 939-944.PubMedCrossRef

23.

Blennow K, Ricksten A, Prince JA, Brookes AJ, Emahazion T, Wasslavik C, Bogdanovic N, Andreasen N, Batsman S, Marcusson J, Nagga K, Wallin A, Regland B, Olofsson H, Hesse C, Davidsson P, Minthon L, Jansson A, Palmqvist L, Rymo L: No association between the alpha2-macroglobulin (A2 M) deletion and Alzheimer's disease, and no change in A2 M mRNA, protein, or protein expression. J Neural Transm. 2000, 107: 1065-1079. 10.1007/s007020070052.PubMedCrossRef

24.

Prince JA, Feuk L, Howell WM, Jobs M, Emahazion T, Blennow K, Brookes AJ: Robust and accurate single nucleotide polymorphism genotyping by dynamic allele-specific hybridization (DASH): design criteria and assay validation. Genome Res. 2001, 11: 152-162. 10.1101/gr.150201.PubMedPubMedCentralCrossRef

25.

Ii K, Ito H, Tanaka K, Hirano A: Immunocytochemical co-localization of the proteasome in ubiquitinated structures in neurodegenerative diseases and the elderly. J Neuropathol Exp Neurol. 1997, 56: 125-131. 10.1097/00005072-199702000-00002.PubMedCrossRef

26.

Mori H, Kondo J, Ihara Y: Ubiquitin is a component of paired helical filaments in Alzheimer's disease. Science. 1987, 235: 1641-1644. 10.1126/science.3029875.PubMedCrossRef

27.

Perry G, Friedman R, Shaw G, Chau V: Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains. Proc Natl Acad Sci USA. 1987, 84: 3033-3036. 10.1073/pnas.84.9.3033.PubMedPubMedCentralCrossRef

28.

Tabaton M, Cammarata S, Mancardi G, Manetto V, Autilio-Gambetti L, Perry G, Gambetti P: Ultrastructural localization of beta-amyloid, tau, and ubiquitin epitopes in extracellular neurofibrillary tangles. Proc Natl Acad Sci USA. 1991, 88: 2098-2102. 10.1073/pnas.88.6.2098.PubMedPubMedCentralCrossRef

29.

Mishto M, Bellavista E, Santoro A, Stolzing A, Ligorio C, Nacmias B, Spazzafumo L, Chiappelli M, Licastro F, Sorbi S, Pession A, Ohm T, Grune T, Franceschi C: Immunoproteasome and LMP2 polymorphism in aged and Alzheimer's disease brains. Neurobiol Aging. 2006, 27: 54-66. 10.1016/j.neurobiolaging.2004.12.004.PubMedCrossRef

30.

Bertram L, Hiltunen M, Parkinson M, Ingelsson M, Lange C, Ramasamy K, Mullin K, Menon R, Sampson AJ, Hsiao MY, Elliott KJ, Velicelebi G, Moscarillo T, Hyman BT, Wagner SL, Becker KD, Blacker D, Tanzi RE: Family-based association between Alzheimer's disease and variants in UBQLN1. N Engl J Med. 2005, 352: 884-894. 10.1056/NEJMoa042765.PubMedCrossRef

31.

Castegna A, Aksenov M, Aksenova M, Thongboonkerd V, Klein JB, Pierce WM, Booze R, Markesbery WR, Butterfield DA: Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part I: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. Free Radic Biol Med. 2002, 33: 562-571. 10.1016/S0891-5849(02)00914-0.PubMedCrossRef

32.

Pasinetti GM: Use of cDNA microarray in the search for molecular markers involved in the onset of Alzheimer's disease dementia. J Neurosci Res. 2001, 65: 471-476. 10.1002/jnr.1176.PubMedCrossRef

33.

Gong B, Cao Z, Zheng P, Vitolo OV, Liu S, Staniszewski A, Moolman D, Zhang H, Shelanski M, Arancio O: Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. Cell. 2006, 126: 775-788. 10.1016/j.cell.2006.06.046.PubMedCrossRef

34.

Beecham GW, Martin ER, Li YJ, Slifer MA, Gilbert JR, Haines JL, Pericak-Vance MA: Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease. Am J Hum Genet. 2009, 84: 35-43. 10.1016/j.ajhg.2008.12.008.PubMedPubMedCentralCrossRef

35.

Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML, Pahwa JS, Moskvina V, Dowzell K, Williams A, Jones N, Thomas C, Stretton A, Morgan AR, Lovestone S, Powell J, Proitsi P, Lupton MK, Brayne C, Rubinsztein DC, Gill M, Lawlor B, Lynch A, Morgan K, Brown KS, Passmore PA, Craig D, McGuinness B, Todd S, Holmes C, et al: Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet. 2009, 41: 1088-1093. 10.1038/ng.440.PubMedPubMedCentralCrossRef

Title: Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) S18Y polymorphism in Alzheimer's disease
Authors: Madeleine Zetterberg
Annica Sjölander
Malin von Otter
Mona Seibt Palmér
Sara Landgren
Lennart Minthon
Anders Wallin
Niels Andreasen
Kaj Blennow
Henrik Zetterberg
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2010
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/1750-1326-5-11

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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