Glucocerebrosidase Mrna Is Diminished In Brain Of Lewy Body Diseases And Changes With Disease Progression In Blood

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 Delta Delta Ct 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

Glucocerebrosidase mRNA is Diminished in Brain of Lewy Body Diseases and Changes with Disease Progression in Blood

Altres ajuts: This work was supported by the Marató TV3 grant 1405/10.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

Glucocerebrosidase Mrna Is Diminished In Brain Of Lewy Body Diseases And Changes With Disease Progression In Blood

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 Delta Delta Ct 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

Impact of 2020 COVID-19 lockdowns on particulate air pollution across Europe

International audienceAbstract. To fight against the first wave of coronavirus disease 2019 (COVID-19) in 2020, lockdown measures were implemented in most European countries. These lockdowns had well-documented effects on human mobility. We assessed the impact of the lockdown implementation and relaxation on air pollution by comparing daily particulate matter (PM), nitrogen dioxide (NO2) and ozone (O3) concentrations, as well as particle number size distributions (PNSDs) and particle light absorption coefficient in situ measurement data, with values that would have been expected if no COVID-19 epidemic had occurred at 28 sites across Europe for the period 17 February–31 May 2020. Expected PM, NO2 and O3 concentrations were calculated from the 2020 Copernicus Atmosphere Monitoring Service (CAMS) ensemble forecasts, combined with 2019 CAMS ensemble forecasts and measurement data. On average, lockdown implementations did not lead to a decrease in PM2.5 mass concentrations at urban sites, while relaxations resulted in a +26 ± 21 % rebound. The impacts of lockdown implementation and relaxation on NO2 concentrations were more consistent (−29 ± 17 and +31 ± 30 %, respectively). The implementation of the lockdown measures also induced statistically significant increases in O3 concentrations at half of all sites (+13 % on average). An enhanced oxidising capacity of the atmosphere could have boosted the production of secondary aerosol at those places. By comparison with 2017–2019 measurement data, a significant change in the relative contributions of wood and fossil fuel burning to the concentration of black carbon during the lockdown was detected at 7 out of 14 sites. The contribution of particles smaller than 70 nm to the total number of particles significantly also changed at most of the urban sites, with a mean decrease of −7 ± 5 % coinciding with the lockdown implementation. Our study shows that the response of PM2.5 and PM10 mass concentrations to lockdown measures was not systematic at various sites across Europe for multiple reasons, the relationship between road traffic intensity and particulate air pollution being more complex than expected