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Aging and disease  2018, Vol. 9 Issue (2): 208-219    DOI: 10.14336/AD.2017.0505
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Glucocerebrosidase mRNA is Diminished in Brain of Lewy Body Diseases and Changes with Disease Progression in Blood
Perez-Roca Laia1, Adame-Castillo Cristina1, Campdelacreu Jaume2, Ispierto Lourdes3, Vilas Dolores3, Rene Ramon2, Alvarez Ramiro3, Gascon-Bayarri Jordi2, Serrano-Munoz Maria A.1, Ariza Aurelio1, Beyer Katrin1,*
1Department of Pathology, Hospital Universitari and Health Sciences Research Institute Germans Trias i Pujol, Universitat Autònoma de Barcelona, Spain
2Department of Neurology, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Spain
3Department of Neurology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
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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.

Key wordsglucocerebrosidase deficiency    Parkinson’s disease    dementia with Lewy bodies    GBA mRNA expression    transcript variants
收稿日期: 2017-02-12      出版日期: 2018-04-01
引用本文:   
. [J]. Aging and disease, 2018, 9(2): 208-219.
Perez-Roca Laia, Adame-Castillo Cristina, Campdelacreu Jaume, Ispierto Lourdes, Vilas Dolores, Rene Ramon, Alvarez Ramiro, Gascon-Bayarri Jordi, Serrano-Munoz Maria A., Ariza Aurelio, Beyer Katrin. Glucocerebrosidase mRNA is Diminished in Brain of Lewy Body Diseases and Changes with Disease Progression in Blood. Aging and disease, 2018, 9(2): 208-219.
链接本文:  
http://www.aginganddisease.org/CN/10.14336/AD.2017.0505      或      http://www.aginganddisease.org/CN/Y2018/V9/I2/208
DiseasenPMtime1 (range)ADstage2Br&Br3Death4 (range)M:F ratio5
pDLB689:30 (3:30-17:00)0-IIA-C74.6 (60-85)3:1
cDLB71210:30 (4:00-21:15)III-VIB-C79.0 (74-86)1.4:1
PD8127:00 (3:30-14:00)III-IV80.8 (68-93)1:1
PDD9137:10 (4:00-12:20)II-VIA-C78.7 (71-87)0.9:1
CTRL10178:40 (2:30-23:30)69.3 (55-81)1.4:1
Table 1  
Name and NCBI1Primer namePrimer sequence (5’ - 3’)Size2
GBA1tv1
NM_000157.3
GBA1tv1U*ATC ACA TGA CCC ATC CAC A214 bp3
GBA1tv1LACT CAA AGG CTT GGG ACA T
GBA1tv2
NM_001005741.2
GBA1tv2U2*TTC GCC GAC GTG GAT CCT CT236 bp
GBA1tv2L2ACC GAG CTG TAG CCG AAG CT
GBA1tv3
NM_001005742.2
GBA1tv3U*TTC GCC GAC GAG ACT CTG GA176 bp
GBA1tv3LACC TGA TGC CCA CGA CAC TG
GBA1tv4
NM_001171811.1
GBA1tv4U*TTC TCT TCG CCG ACG GTG CC169 bp
GBA1tv4LAGC TCC ATC CGT CGC CCA CT
GBA1tv5
NM_001171812.1
GBA1tv5U*ACG GGC ACA GGA ATC GGA TA173 bp
GBA1tv5LAAC TGC AGG GCT CGG TGA AT
b-act U2TCT ACA ATG AGC TGC GTG TG228 bp4
b-act L2GGA TAG CAA CGT ACA TGG CT
b-act U3AAC TGG GAC GAC ATG GAG AA178 bp5
b-act L3TAG ATG GGC ACA GTG TGG GT
GUS6-U1ATG TGG TTG GAG AGC TCA TT176 bp
GUS-L2TGT CTC TGC CGA GTG AAG AT
PBGD7_U1ACA CAC AGC CTA CTT TCC AAG183 bp
PBGD_L1TCA ATG TTG CCA CCA CAC TGT
Table 2  
Figure 1.  
Figure 2.  
Figure 3.  
Figure 4.  
DLB
Disease onset<65 years>65 yearsP1
n614
age at onset (range)61.4 (59-65)68.5 (66-74)n.p.2
age (range)67.6 (63-71)73.8 (69-80)n.p.
duration (range)6.2 (2-10)4.9 (2-10)0.135
male: female ratio1: 0.331: 0.40.765
Disease duration since onset<6 years>6 years
n137
age at onset (range)67.1 (59-74)63.5 (60-67)0.238
age (range)70.8 (63-80)72.8 (70-77)0.302
male:female ratio1: 0.51: 0.250.097
PD
Disease onset<65 years>65 years
n1214
age at onset (range)62.2 (60-64)70.0 (68-73)n.p.
age (range)69.0 (61-75)72.5 (68-75)n.p.
duration (range)6.8 (1-14)2.5 (0-6)0.015
male: female ratio1: 0.81:010.827
Disease duration since onset<6 years>6 years
n1511
age at onset (range)66.9 (60-73)61.7 (60-64)0.105
age (range)69.6 (61-75)72.3 (68-75)0.376
male: female ratio1: 0.91: 0.91
Table 3  
Figure 5.  
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