Glucocerebrosidase mRNA is Diminished in Brain of Lewy Body Diseases and Changes with Disease Progression in Blood
Pérez-Roca, Laia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Adame Castillo, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Campdelacreu, Jaume (Hospital Universitari de Bellvitge)
Ispierto, Lourdes (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Vilas, Dolores (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Rene, Ramon (Hospital Universitari de Bellvitge)
Álvarez, Ramiro (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Gascon-Bayarri, Jordi (Hospital Universitari de Bellvitge)
Serrano-Munoz, Maria A. (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ariza Fernández, A.. (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Beyer, Katrin (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Date:	2018
Abstract:	Parkinson disease (PD) and dementia with Lewy bodies (DLB) are Lewy body diseases characterized by abnormal alpha-synuclein deposits and overlapping pathological features in the brain. Several studies have shown that glucocerebrosidase (GBA) deficiency is involved in the development of LB diseases. Here, we aimed to find out if this deficiency starts at the transcriptional level, also involves alternative splicing, and if GBA expression changes in brain are also detectable in blood of patients with LB diseases. The expression of three GBA transcript variants (GBAtv1, GBAtv2 and GBAtv5) was analyzed in samples from 20 DLB, 25 PD and 17 control brains and in blood of 20 DLB, 26 PD patients and 17 unaffected individuals. Relative mRNA expression was determined by real-time PCR. Expression changes were evaluated by the ΔΔCt method. In brain, specific expression profiles were identified in the temporal cortex of DLB and in the caudate nucleus of PD. In blood, significant GBA mRNA diminution was found in both DLB and PD patients. Early PD and early-onset DLB patients showed lowest GBA levels which were normal in PD patients with advanced disease and DLB patients who developed disease after 70 years of age. In conclusion, disease group specific GBA expression profiles were found in mostly affected areas of LBD. In blood, GBA expression was diminished in LB diseases, especially in patients with early onset DLB and in patients with early PD. Age of disease onset exerts an opposite effect on GBA expression in DLB and PD.
Note:	Altres ajuts: This work was supported by the Marató TV3 grant 1405/10.
Note:	Altres ajuts: MSCBS/PI12-1702
Note:	Altres ajuts: MSCBS/PI15-216
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Glucocerebrosidase deficiency ; Parkinson's disease ; Dementia with Lewy bodies ; GBA mRNA expression ; Transcript variants
Published in:	Aging and Disease, Vol. 9 (april 2018) , p. 208-219, ISSN 2152-5250

DOI: 10.14336/AD.2017.0505
PMID: 29896411

12 p, 592.9 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
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