Journal ArticleDOI
Cerebellar alpha-synuclein levels are decreased in Parkinson's disease and do not correlate with SNCA polymorphisms associated with disease in a Swedish material.
Marie Westerlund,Andrea Carmine Belin,Anna Anvret,Anna Håkansson,Hans Nissbrandt,Charlotta Lind,Olof Sydow,Lars Olson,Dagmar Galter +8 more
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TLDR
These findings demonstrate that the investigated Parkinson patients have markedly reduced levels of α‐synuclein in cerebellum, and that this reduction is general, rather then correlated to the investigated polymorphisms, although two of the polymorphisms also associated with disease in a Swedish material.Abstract:
Alterations of brain and plasma alpha-synuclein levels and SNCA gene variability have been implicated in the pathogenesis of Parkinson's disease (PD). We therefore measured alpha-synuclein protein levels in postmortem PD and control cerebellum tissue using Western blot and investigated whether the levels correlated to SNCA genotype. We found markedly decreased alpha-synuclein levels in PD patients (n=16) compared to gender- and age-matched controls (n=14; P=0.004) normalized to alpha-tubulin. We also performed an association study of the noncoding polymorphisms rs2737029 (A/G) and rs356204 (A/G) (intron 4), and of rs356219 (T/C) (3'-region) of SNCA in a Swedish PD case-control material. Using a two-sided chi(2) test, we found significant association of rs2737029 (P=0.003; chi(2)=9.07) and rs356204 (P=0.048; chi(2)=3.91) with disease, strengthening the involvement of SNCA polymorphisms in sporadic PD. Stratification of the human postmortem brain material by genotype of the three investigated polymorphisms, did not indicate any influence of genotype on alpha-synuclein protein levels when comparing PD with controls. Taken together, our findings demonstrate that the investigated Parkinson patients have markedly reduced levels of alpha-synuclein in cerebellum, and that this reduction is general, rather then correlated to the investigated polymorphisms, although two of the polymorphisms also associated with disease in a Swedish material.read more
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Journal ArticleDOI
The cerebellum in Parkinson’s disease
Tao Wu,Mark Hallett +1 more
TL;DR: The role of the cerebellum in Parkinson's disease is investigated in this paper, where functional or morphological modulations were detected related to akinesia/rigidity, tremor, gait disturbance, dyskinesia and some non-motor symptoms.
Journal ArticleDOI
DJ-1 and α-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease
Zhen Hong,Min Shi,Kathryn A. Chung,Joseph F. Quinn,Elaine R. Peskind,Douglas Galasko,Joseph Jankovic,Cyrus P. Zabetian,James B. Leverenz,Geoffrey S. Baird,Thomas J. Montine,Aneeka M. Hancock,Hyejin Hwang,Catherine Pan,Joshua M. Bradner,Un Jung Kang,Poul Henning Jensen,Jing Zhang +17 more
TL;DR: It is demonstrated that total DJ-1 and alpha-synuclein in human cerebrospinal fluid are helpful diagnostic markers for Parkinson's disease, if variables such as blood contamination and age are taken into consideration.
Journal ArticleDOI
Glucocerebrosidase deficiency in substantia nigra of parkinson disease brains
Matthew E. Gegg,Derek Burke,Derek Burke,Simon J.R. Heales,Simon J.R. Heales,J. Mark Cooper,John Hardy,Nicholas W. Wood,Anthony H.V. Schapira +8 more
TL;DR: This work investigated the enzymatic activity of glucocerebrosidase (GCase) in PD brains carrying heterozygote GBA mutations (PD+GBA) and sporadic PD brains.
Journal ArticleDOI
Alpha-synuclein in the cerebrospinal fluid differentiates synucleinopathies (Parkinson Disease, dementia with Lewy bodies, multiple system atrophy) from Alzheimer disease.
TL;DR: The results of the present study suggest that quantification of CSF SNCA helps in the differentiation of synucleinopathies (PD, DLB, and MSA) from AD, however, CSFSNCA levels did not differ significantly among the 3 synucle inopathies.
Journal ArticleDOI
Association of Nrf2-encoding NFE2L2 haplotypes with Parkinson's disease.
Malin von Otter,Sara Landgren,Staffan Nilsson,Dragana Celojevic,Petra Bergström,Anna Håkansson,Hans Nissbrandt,Marek Drozdzik,Monika Białecka,Mateusz Kurzawski,Kaj Blennow,Michael Nilsson,Ola Hammarsten,Henrik Zetterberg +13 more
TL;DR: It is suggested that variation in NFE2L2 modifies the Parkinson's disease process and provide another link between oxidative stress and neurodegeneration.
References
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Journal ArticleDOI
Mutation in the α-synuclein gene identified in families with Parkinson's disease
Mihael H. Polymeropoulos,Christian Lavedan,Elisabeth Leroy,Susan E. Ide,Anindya Dehejia,Amalia Dutra,Brian L. Pike,Holly Root,Jeffrey Rubenstein,Rebecca Boyer,Edward S. Stenroos,Settara C. Chandrasekharappa,Aglaia Athanassiadou,Theodore Papapetropoulos,William G. Johnson,Alice Lazzarini,Roger C. Duvoisin,Giuseppe Di Iorio,Lawrence I. Golbe,Robert L. Nussbaum +19 more
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Journal ArticleDOI
α-Synuclein Locus Triplication Causes Parkinson's Disease
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Journal ArticleDOI
Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease.
Rejko Krüger,Wilfried Kuhn,Thomas Müller,Dirk Woitalla,Manuel B. Graeber,Sigfried Kösel,Horst Przuntek,Jörg T. Epplen,Ludger Schöls,Olaf Riess +9 more
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The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia.
Juan J. Zarranz,Javier Alegre,Juan Carlos Gómez-Esteban,Elena Lezcano,Raquel Ros,Israel Ampuero,Lídice Vidal,Janet Hoenicka,Olga Rodriguez,Begoña Atarés,Verónica Llorens,Estrella Gomez Tortosa,Teodoro del Ser,David G. Munoz,Justo García de Yébenes +14 more
TL;DR: Dementia with Lewy bodies is related to mutation of α‐synuclein, and the novel mutation, that substitutes a dicarboxylic amino acid, glutamic acid, with a basic amino acid in a much conserved area of the protein, is likely to produce severe disturbance of protein function.
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