Prion diseases in Denmark: Molecular characterization and investigation of CNS microenvironment (2019)

Abstract

Prion diseases are transmissible neurodegenerative diseases caused by prions, which are host-encoded, misfolded cellular prion proteins. Prion diseases are unique because they can be acquired, genetic, or sporadic and present heterogenous phenotypes. Molecular characterization of these phenotypes is essential for enhanced prion disease diagnostics, classification, and understanding of their pathogenesis. 

An important role in prion disease neurodegeneration is played by the brain's resident innate immune cells called microglia, which are responsible for chronic neuroinflammation, causing the brain damage. Interestingly, microglia are a very diverse cell population, multiple phenotypes of which may be defined by a variety of factors present in their microenvironment. 

Thus, the aim of this PhD project was to 1) characterize and re-classify all available fresh frozen brain samples of human prion disease referred to the Danish Reference Center for Prion Diseases (DRCPD) by using improved molecular diagnostics and the latest prion disease classification recommendations; and 2) to investigate regional and neuroinflammatory brain microenvironment differences in sporadic Creutzfeldt-Jakob disease patients.

Danish prio disease cohort characterization revealed several intriguing, novel, and unique cases; whereas brain microenvironment investigation indicated regionally and sub-regionally distinct gene expression, suggesting a variable neuroinflammatory response. All the findings were published in peer reviewed journals and can be accessed via links below.

Additional project information

The project was carried out at the Danish Reference Center for Prion Disease, Department of Pathology, Copenhagen University Hospital and in collaboration with the University of Edinburgh, UK and University of Bologna, Italy

Place of employment

Department of Pathology

PhD author

Ausrine Areskeviciute, MSc, PhD

Date and place of defense

29th November 2019, Department of Clinical Medicine, University of Copenhagen

Supervisors

Eva Charlotte Løbner Lund (main)
Helle Broholm
Linea Cecilie Melchior

Links

ordcid.org
mdpi.com
Article on academic.oup.com
Article on academic.oup.com
Article on academic.oup.com




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