Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/121212
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Type: Journal article
Title: Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies
Author: Bras, J.
Guerreiro, R.
Darwent, L.
Parkkinen, L.
Ansorge, O.
Escott-Price, V.
Hernandez, D.G.
Nalls, M.A.
Clark, L.N.
Honig, L.S.
Marder, K.
Van Der Flier, W.M.
Lemstra, A.
Scheltens, P.
Rogaeva, E.
St George-Hyslop, P.
Londos, E.
Zetterberg, H.
Ortega-Cubero, S.
Pastor, P.
et al.
Citation: Human Molecular Genetics, 2014; 23(23):6139-6146
Publisher: Oxford University Press
Issue Date: 2014
ISSN: 0964-6906
1460-2083
Statement of
Responsibility: 
Jose Bras, Rita Guerreiro, Lee Darwent, Laura Parkkinen, Olaf Ansorge ... Tamas Revesz ... et al.
Abstract: Clinical and neuropathological similarities between dementia with Lewy bodies (DLB), Parkinson's and Alzheimer's diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis, we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). The results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after a study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in PD. We have previously shown that the p.N370S variant in GBA is associated with DLB, which, together with the findings at the SCARB2 locus, suggests a role for lysosomal dysfunction in this disease. These results indicate that DLB has a unique genetic risk profile when compared with the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder. We make all these data available.
Keywords: Parkinson disease; alzheimer's disease; lewy body disease; apolipoproteine; genome; lysosomes; neurodegenerative disorders; genetic analysis; alpha-synuclein; genetic risk; misdiagnosis; causality
Rights: © The Author 2014. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ .0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
RMID: 0030128200
DOI: 10.1093/hmg/ddu334
Appears in Collections:Genetics publications

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