Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's

Autor: Liu, Ganqiang, Boot, Brendon, Cormier-Dequaire, Florence, Corvol, Jean-Christophe, Barker, Roger A, Heutink, Peter, Marinus, Johan, Williams-Gray, Caroline H, Scherzer, Clemens R, Progression, International Genetics of Parkinson Disease, Scherzer, C., Hyman, B. T., Locascio, Joseph J, Ivinson, A. J., Trisini-Lipsanopoulos, A., Franco, D., Burke, K., Sudarsky, L. R., Hayes, M. T., Umeh, C. C., Growdon, J. H., Schwarzschild, M. A., Hung, A. Y., Jansen, Iris E, Flaherty, A. W., Wills, A-M, Mejia, N. I., Gomperts, S. N., Khurana, V., Selkoe, D. J., Yi, T., Page, K., Liao, Z., Barker, R., Winder-Rhodes, Sophie, Foltynie, T., Williams-Gray, C. H., Mason, S., Winder-Rhodes, S., Breen, D., Cummins, G., Evans, J., Eberly, Shirley, Corvol, J-C, Brice, A., Elbaz, A., Mallet, A., Vidailhet, M., Bonnet, A-M, Bonnet, C., Grabli, D., Hartmann, A., Klebe, S., Elbaz, Alexis, Lacomblez, L., Mangone, G., Bourdain, F., Brandel, J-P, Derkinderen, P., Durif, F., Mesnage, V., Pico, F., Rascol, O., Forlani, S., Brice, Alexis, Lesage, S., Tahiri, K., van Hilten, J. J., Marinus, J., Duong, K., Ravina, Bernard, Dong, X., Hutten, S. J., Amr, S. S., Shoulson, I., Tanner, C. M., Lang, A. E., Nalls, M. A., van Hilten, Jacobus J
Přispěvatelé: Human genetics, Amsterdam Neuroscience - Neurodegeneration, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hertie Institute for Clinical Brain Research [Tubingen], University of Tübingen, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Oncology
medicine.medical_specialty
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Disease
medicine.disease_cause
genetics [Glucosylceramidase]
etiology [Cognitive Dysfunction]
03 medical and health sciences
0302 clinical medicine
Parkinson Disease/complications
genetics [Parkinson Disease]
Internal medicine
Genetic variation
medicine
Humans
Cognitive Dysfunction/etiology
ddc:610
Longitudinal Studies
Cognitive decline
Allele
ComputingMilieux_MISCELLANEOUS
Aged
Aged
80 and over
Genetics
genetics [Gaucher Disease]
Mutation
[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior
Proportional hazards model
[SCCO.NEUR]Cognitive science/Neuroscience
Hazard ratio
genetics [Cognitive Dysfunction]
[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences
Middle Aged
Confidence interval
3. Good health
030104 developmental biology
Neurology
Glucosylceramidase/genetics
Disease Progression
Glucosylceramidase
Female
Neurology (clinical)
complications [Gaucher Disease]
complications [Parkinson Disease]
Gaucher Disease/complications
Psychology
030217 neurology & neurosurgery
Zdroj: Annals of Neurology, 80(5), 674-685. John Wiley and Sons Inc.
Annals of Neurology
Annals of Neurology, Wiley, 2016, 80 (5), pp.674-685. ⟨10.1002/ana.24781⟩
Liu, G, Boot, B, Locascio, J J, Jansen, I E, Winder-Rhodes, S, Eberly, S, Elbaz, A, Brice, A, Ravina, B, van Hilten, J J, Cormier-Dequaire, F, Corvol, J C, Barker, R A, Heutink, P, Marinus, J, Williams-Gray, C H, Scherzer, C R, Scherzer, C, Hyman, B T, Ivinson, A J, Trisini-Lipsanopoulos, A, Franco, D, Burke, K, Sudarsky, L R, Hayes, M T, Umeh, C C, Growdon, J H, Schwarzschild, M A, Hung, A Y, Flaherty, A W, Wills, A M, Mejia, N I, Gomperts, S N, Khurana, V, Selkoe, D J, Yi, T, Page, K, Liao, Z, Barker, R, Foltynie, T, Williams-Gray, C H, Mason, S, Winder-Rhodes, S, Barker, R, Williams-Gray, C H, Breen, D, Cummins, G, Evans, J, Winder-Rhodes, S, Corvol, J C, Brice, A, Elbaz, A, Mallet, A, Vidailhet, M, Bonnet, A M, Bonnet, C, Grabli, D, Hartmann, A, Klebe, S, Lacomblez, L, Mangone, G, Bourdain, F, Brandel, J P, Derkinderen, P, Durif, F, Mesnage, V, Pico, F, Rascol, O, Forlani, S, Lesage, S, Tahiri, K, van Hilten, J J, Marinus, J, Liao, Z, Page, K, Franco, D, Duong, K, Yi, T, Trisini-Lipsanopoulos, A, Dong, X, Sudarsky, L R, Hutten, S J, Amr, S S, Shoulson, I, Tanner, C M, Lang, A E & Nalls, M A 2016, ' Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's ', Annals of Neurology, vol. 80, no. 5, pp. 674-685 . https://doi.org/10.1002/ana.24781
Annals of neurology 80(5), 674-685 (2016). doi:10.1002/ana.24781
Annals of Neurology, 2016, 80 (5), pp.674-685. ⟨10.1002/ana.24781⟩
Annals of Neurology, 80(5), 674-685
2016, ' Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's ', Annals of Neurology, vol. 80, no. 5, pp. 674-685 . https://doi.org/10.1002/ana.24781
ISSN: 0364-5134
1531-8249
DOI: 10.1002/ana.24781⟩
Popis: 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.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.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.INTERPRETATION: 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.
Databáze: OpenAIRE
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