Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's.
Identifieur interne : 000077 ( PubMed/Checkpoint ); précédent : 000076; suivant : 000078Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's.
Auteurs : Ganqiang Liu [États-Unis] ; Brendon Boot [États-Unis] ; Joseph J. Locascio [États-Unis] ; Iris E. Jansen [Pays-Bas] ; Sophie Winder-Rhodes [Royaume-Uni] ; Shirley Eberly [États-Unis] ; Alexis Elbaz [France] ; Alexis Brice [France] ; Bernard Ravina [États-Unis] ; Jacobus J. Van Hilten [Pays-Bas] ; Florence Cormier-Dequaire [France] ; Jean-Christophe Corvol [France] ; Roger A. Barker [Royaume-Uni] ; Peter Heutink [Pays-Bas] ; Johan Marinus [Pays-Bas] ; Caroline H. Williams-Gray [Royaume-Uni] ; Clemens R. Scherzer [États-Unis]Source :
- Annals of neurology [ 1531-8249 ] ; 2016.
Abstract
We hypothesized that specific mutations in the β-glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non-neuropathic GD mutations confer intermediate progression rates.
DOI: 10.1002/ana.24781
PubMed: 27717005
Affiliations:
- France, Pays-Bas, Royaume-Uni, États-Unis
- Angleterre, Angleterre de l'Est, Hollande-Méridionale, Massachusetts, État de New York, Île-de-France
- Cambridge, Leyde, Paris
- Université de Cambridge
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<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
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<author><name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name>
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<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Medical Genomics, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, HZ</wicri:regionArea>
<wicri:noRegion>HZ</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Marinus, Johan" sort="Marinus, Johan" uniqKey="Marinus J" first="Johan" last="Marinus">Johan Marinus</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Neurology, Leiden University Medical Center, Leiden</wicri:regionArea>
<placeName><settlement type="city">Leyde</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
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<author><name sortKey="Williams Gray, Caroline H" sort="Williams Gray, Caroline H" uniqKey="Williams Gray C" first="Caroline H" last="Williams-Gray">Caroline H. Williams-Gray</name>
<affiliation wicri:level="4"><nlm:affiliation>John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge</wicri:regionArea>
<orgName type="university">Université de Cambridge</orgName>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
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<author><name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens R" last="Scherzer">Clemens R. Scherzer</name>
<affiliation wicri:level="2"><nlm:affiliation>Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham & Women's Hospital, Cambridge, MA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham & Women's Hospital, Cambridge</wicri:cityArea>
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<series><title level="j">Annals of neurology</title>
<idno type="eISSN">1531-8249</idno>
<imprint><date when="2016" type="published">2016</date>
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<front><div type="abstract" xml:lang="en">We hypothesized that specific mutations in the β-glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non-neuropathic GD mutations confer intermediate progression rates.</div>
</front>
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<pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">27717005</PMID>
<DateCreated><Year>2016</Year>
<Month>10</Month>
<Day>07</Day>
</DateCreated>
<DateRevised><Year>2017</Year>
<Month>01</Month>
<Day>27</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1531-8249</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>80</Volume>
<Issue>5</Issue>
<PubDate><Year>2016</Year>
<Month>Nov</Month>
</PubDate>
</JournalIssue>
<Title>Annals of neurology</Title>
<ISOAbbreviation>Ann. Neurol.</ISOAbbreviation>
</Journal>
<ArticleTitle>Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's.</ArticleTitle>
<Pagination><MedlinePgn>674-685</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1002/ana.24781</ELocationID>
<Abstract><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">We hypothesized that specific mutations in the β-glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non-neuropathic GD mutations confer intermediate progression rates.</AbstractText>
<AbstractText Label="METHODS" NlmCategory="METHODS">A total of 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median, 4.1) from seven cohorts were analyzed. Differential effects of four types of genetic variation in GBA on longitudinal cognitive decline were evaluated using mixed random and fixed effects and Cox proportional hazards models.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">Overall, 10.3% of patients with PD and GBA sequencing carried a mutation. Carriers of neuropathic GD mutations (1.4% of patients) had hazard ratios (HRs) for global cognitive impairment of 3.17 (95% confidence interval [CI], 1.60-6.25) and a hastened decline in Mini-Mental State Exam scores compared to noncarriers (p = 0.0009). Carriers of complex GBA alleles (0.7%) had an HR of 3.22 (95% CI, 1.18-8.73; p = 0.022). By contrast, the common, non-neuropathic N370S mutation (1.5% of patients; HR, 1.96; 95% CI, 0.92-4.18) or nonpathogenic risk variants (6.6% of patients; HR, 1.36; 95% CI, 0.89-2.05) did not reach significance.</AbstractText>
<AbstractText Label="INTERPRETATION" NlmCategory="CONCLUSIONS">Mutations in the GBA gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into "high gear." These findings suggest a relationship between specific types of GBA mutations and aggressive cognitive decline and have direct implications for improving the design of clinical trials. Ann Neurol 2016;80:674-685.</AbstractText>
<CopyrightInformation>© 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Liu</LastName>
<ForeName>Ganqiang</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham & Women's Hospital, Cambridge, MA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>Brendon</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Neurology, Brigham and Women's Hospital, Boston, MA.</Affiliation>
</AffiliationInfo>
</Author>
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<Initials>JJ</Initials>
<AffiliationInfo><Affiliation>Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham & Women's Hospital, Cambridge, MA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Neurology, Massachusetts General Hospital, Boston, MA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jansen</LastName>
<ForeName>Iris E</ForeName>
<Initials>IE</Initials>
<AffiliationInfo><Affiliation>Department of Medical Genomics, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, HZ, The Netherlands.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>German Center for Neurodegenerative diseases (DZNE), Tübingen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
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<AffiliationInfo><Affiliation>John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>Shirley</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>Alexis</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>INSERM, Centre for Research in Epidemiology and Population Health, U1018, Epidemiology of ageing and age related diseases, Villejuif, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>University Paris-Sud, UMRS 1018, Villejuif, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Brice</LastName>
<ForeName>Alexis</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Sorbonne Université, Université Pierre et Marie Curie Paris 06 UMR S 1127, Institut National de Santé et en Recherche Médicale U 1127 and Centre d'Investigation Clinique 1422, Centre National de Recherche Scientifique U 7225, Institut du Cerveau et de la Moelle Epinière, Assistance Publique Hôpitaux de Paris, Département de Neurologie et de Génétique, Hôpital Pitié-Salpêtrière, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ravina</LastName>
<ForeName>Bernard</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Voyager Therapeutics, Clinical Development, Cambridge, MA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>van Hilten</LastName>
<ForeName>Jacobus J</ForeName>
<Initials>JJ</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cormier-Dequaire</LastName>
<ForeName>Florence</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Sorbonne Université, Université Pierre et Marie Curie Paris 06 UMR S 1127, Institut National de Santé et en Recherche Médicale U 1127 and Centre d'Investigation Clinique 1422, Centre National de Recherche Scientifique U 7225, Institut du Cerveau et de la Moelle Epinière, Assistance Publique Hôpitaux de Paris, Département de Neurologie et de Génétique, Hôpital Pitié-Salpêtrière, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Corvol</LastName>
<ForeName>Jean-Christophe</ForeName>
<Initials>JC</Initials>
<AffiliationInfo><Affiliation>Sorbonne Université, Université Pierre et Marie Curie Paris 06 UMR S 1127, Institut National de Santé et en Recherche Médicale U 1127 and Centre d'Investigation Clinique 1422, Centre National de Recherche Scientifique U 7225, Institut du Cerveau et de la Moelle Epinière, Assistance Publique Hôpitaux de Paris, Département de Neurologie et de Génétique, Hôpital Pitié-Salpêtrière, Paris, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Barker</LastName>
<ForeName>Roger A</ForeName>
<Initials>RA</Initials>
<AffiliationInfo><Affiliation>John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Heutink</LastName>
<ForeName>Peter</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Department of Medical Genomics, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, HZ, The Netherlands.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>German Center for Neurodegenerative diseases (DZNE), Tübingen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Marinus</LastName>
<ForeName>Johan</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Williams-Gray</LastName>
<ForeName>Caroline H</ForeName>
<Initials>CH</Initials>
<AffiliationInfo><Affiliation>John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Scherzer</LastName>
<ForeName>Clemens R</ForeName>
<Initials>CR</Initials>
<AffiliationInfo><Affiliation>Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham & Women's Hospital, Cambridge, MA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Neurology, Brigham and Women's Hospital, Boston, MA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Neurology, Massachusetts General Hospital, Boston, MA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><CollectiveName>International Genetics of Parkinson Disease Progression (IGPP) Consortium</CollectiveName>
</Author>
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<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>R01 NS024778</GrantID>
<Acronym>NS</Acronym>
<Agency>NINDS NIH HHS</Agency>
<Country>United States</Country>
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<Grant><GrantID>U01 NS050095</GrantID>
<Acronym>NS</Acronym>
<Agency>NINDS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>U01 NS082157</GrantID>
<Acronym>NS</Acronym>
<Agency>NINDS NIH HHS</Agency>
<Country>United States</Country>
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<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Ann Neurol</MedlineTA>
<NlmUniqueID>7707449</NlmUniqueID>
<ISSNLinking>0364-5134</ISSNLinking>
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<li>Angleterre de l'Est</li>
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<li>Massachusetts</li>
<li>État de New York</li>
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<settlement><li>Cambridge</li>
<li>Leyde</li>
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<orgName><li>Université de Cambridge</li>
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<tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Liu, Ganqiang" sort="Liu, Ganqiang" uniqKey="Liu G" first="Ganqiang" last="Liu">Ganqiang Liu</name>
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<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Winder Rhodes, Sophie" sort="Winder Rhodes, Sophie" uniqKey="Winder Rhodes S" first="Sophie" last="Winder-Rhodes">Sophie Winder-Rhodes</name>
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<name sortKey="Williams Gray, Caroline H" sort="Williams Gray, Caroline H" uniqKey="Williams Gray C" first="Caroline H" last="Williams-Gray">Caroline H. Williams-Gray</name>
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<country name="France"><noRegion><name sortKey="Elbaz, Alexis" sort="Elbaz, Alexis" uniqKey="Elbaz A" first="Alexis" last="Elbaz">Alexis Elbaz</name>
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<name sortKey="Corvol, Jean Christophe" sort="Corvol, Jean Christophe" uniqKey="Corvol J" first="Jean-Christophe" last="Corvol">Jean-Christophe Corvol</name>
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