PhD defence H. (Hata) Karamujić-Čomić

Below is a brief summary of the dissertation:

In this thesis, different molecular approaches are used to discover novel insights into the pathophysiology of dementia and related endophenotypes. The epidemiology of prion diseases is described, showing an increased incidence of 1.8 patients per million per year. Further, the role of specific genetic variants, blood-based metabolites, and gut microbiota in relation to dementia, Alzheimer’s disease, aging, and neurodegenerative and neurovascular brain traits is explored. Lower concentrations of leucine, valine, omega-6 fatty acids, 18:2 linoleic acid, and small very low density lipoprotein subclasses are associated with incident dementia. Further, higher concentrations of glutamine are associated with prevalent dementia, whereas lower concentrations of tyrosine, valine, 22:6 docosahexaenoic acid, and omega-3 fatty acids are associated with prevalent dementia. Higher concentrations of glucose are associated with white matter hyperintensities, brain atrophy, and lateral ventricular volume. With regards to the role of microbiota, genus Clostridium sensu stricto 1 and family Clostridiaceae 1 are associated with better cognitive function, larger global brain volume, and less white matter hyperintensities. As metabolites and microbiota are diet-related and modifiable, this is a promising research field. Further integration of omics data will have an important role in future research, aiming to lead to novel insights leading to improved diagnostics and development of personalized prevention programs and treatments.