Epigenetic modulation of<i> AREL1</i> and increased <i>HLA</i> expression in brains of multiple system atrophy patients

International audienceMultiple system atrophy (MSA) is a rare disease with a fatal outcome. To date, little is known about the molecular processes underlying disease development. Its clinical overlap with related neurodegenerative movement disorders underlines the importance for expanding the knowledge of pathological brain processes in MSA patients to improve distinction from similar diseases. In the current study, we investigated DNA methylation changes in brain samples from 41 MSA patients and 37 healthy controls. We focused on the prefrontal cortex, a moderately affected area in MSA. Using Illumina MethylationEPIC arrays, we investigated 5-methylcytosine (5mC) as well as 5-hydroxymethylcytosine (5hmC) changes throughout the genome. We identified five significantly different 5mC probes (adj. P < 0.05), of which one probe mapping to the AREL1 gene involved in antigen presentation was decreased in MSA patients. This decrease correlated with increased 5hmC levels. Further, we identified functional DNA methylation modules involved in inflammatory processes. As expected, the decreased 5mC levels on AREL1 was concordant with increased gene expression levels of both AREL1 as well as MHC Class I HLA genes in MSA brains. We also investigated whether these changes in antigen-related processes in the brain associated with changes in peripheral mononuclear cells. Using flow cytometry on an independent cohort of MSA patients, we identified a decrease in circulating non-classical CD14+CD16++ blood monocytes, whereas T and NK cell populations were unchanged. Taken together, our results support the view of an active neuroimmune response in brains of MSA patients

Access and Use of Device-Aided Therapies for Parkinson’s Disease in Denmark

BACKGROUND: In Denmark’s five regions, there is potential inequality in access to device‐aided therapy (DAT) for Parkinson’s disease (PD) based on structural or socioeconomic factors. It is unclear how long DAT is maintained and affects concomitant medication. OBJECTIVES: To investigate access to DAT by comparing the proportion of patients with DBS, subcutaneous apomorphine infusion (SCAI), or levodopa/carbidopa intestinal gel (LCIG) in Danish regions 2008–2016 and describe demographics of patients, changes in use of comedication, and maintenance of DAT. METHODS: This work is a retrospective nationwide population‐based registry analysis generated by combining various registries and statistics in Denmark. RESULTS: From 2008 to 2016, 612 patients started DAT. There were statistically significant differences in the number of patients starting DAT between the Capital Region (99.5 per 1,000) and both Central Jutland (66.6 per 1,000) and North Jutland (70.6 per 1,000; P < 0.05). Among DBS and LCIG patients, respectively, 4% and 42% were aged ≥70 years, 68% and 63% were men (vs. 59% in the general PD population; P < 0.05 for DBS), 73% and 63% had a partner (vs. 62% in the general PD population), and 73% and 71% had a qualifying education (vs. 63% in the general PD population; P < 0.05). Use of PD‐related medication decreased significantly from 4 years before to 4 years after DAT. Eighty‐one percent of the patients who started LCIG, alive 4 years later, had maintained this treatment. CONCLUSIONS: There is unequal access to DAT in the Danish regions, and political and social considerations are warranted to address structural and socioeconomic causes