Deciphering cellular heterogeneity of the brain: implications for neurodegenerative diseases

Emma Gerrits

    Research output: ThesisThesis fully internal (DIV)

    1072 Downloads (Pure)

    Abstract

    The brain is a complex and sophisticated organ and comprises over 100 billion neurons, with an even larger number of supporting cells (glia) and a multicellular vascular architecture. The aim of this thesis was to decipher cellular heterogeneity of human brain tissues affected by neurodegenerative diseases.
    In chapter 1, the cellular composition of the brain is reviewed, as well as subcellular heterogeneity and the involvement of subtypes in neurodegenerative diseases. In chapter 2 we studied MS brain tissues with scRNAseq and showed that brain macrophages adopt several distinct phenotypes in MS that are associated with stress, demyelination and inflammation. In chapter 3 we investigated whether snRNAseq is a reliable proxy for scRNAseq. We showed that snRNAseq of microglia results in reliable transcriptomics data that can be used to study frozen brain tissues. In chapter 4 we studied LOAD brain tissues using snRNAseq and showed that microglia adopt distinct profiles that associate with either amyloid-b or tau pathology. In chapter 5 we studied FTD-GRN brain tissues and showed that astrocytes, endothelial cells and mural cells were severely affected. These data indicate that neurovascular changes underlie neurodegeneration in FTD-GRN and should be considered a prime target of future studies and therapies for FTD-GRN. In chapter 6 a summary and discussion of the findings reported in this thesis and future perspectives are presented. Together, these data contribute to our understanding of neurodegenerative diseases and will help to identify new biomarkers and targets for therapies to monitor, reduce or halt disease onset and progression.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Boddeke, Erik, Supervisor
    • Eggen, Bart, Supervisor
    • Kooistra, Susanne, Co-supervisor
    Award date7-Feb-2022
    Place of Publication[Groningen]
    Publisher
    DOIs
    Publication statusPublished - 2022

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