Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital

Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


  1. Locus coeruleus pathology in progressive supranuclear palsy, and its relation to disease severity

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. TDP-43-specific Autoantibody Decline in Patients With Amyotrophic Lateral Sclerosis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Paroxysmal Cranial Dyskinesia and Nail-Patella Syndrome Caused by a Novel Variant in the LMX1B Gene

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Deep Brain Stimulation in Parkinson's Disease: Still Effective After More Than 8 Years

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Normal pressure hydrocephalus secondary to Lyme disease, a case report and review of seven reported cases

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

Vis graf over relationer

Multiple 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.

TidsskriftActa neuropathologica communications
Udgave nummer1
Sider (fra-til)29
StatusUdgivet - 9 mar. 2020

ID: 59672613