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Neurodegeneration-associated tau protein in the human developing brain

Jasna Jarc (2016) Neurodegeneration-associated tau protein in the human developing brain. MSc thesis.

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    The concept of my thesis is based on the link between disorders of neural development and age-related neurodegeneration. As the world population is becoming older, we are facing an increasing number of individuals with serious cognitive impairments. However, there are no clinical markers to predict neither who nor when will one develop such an impairment. Recent research revealed that practically all individuals with a genetic cause of intellectual disability (Down syndrome (DS) individuals) will develop Alzheimer’s disease (AD)-like pathology in the course of their life. Thus, a link between neural development and ageing was proposed. Indeed, a transient physiological phosphorylation of tau is reported at some phosphorylatable epitopes during normal brain development. These epitopes are normally seen to be hyperphosphorylated in AD. Thus, the aim of this thesis was to investigate the patterns of tau phosphorylation during normal development and in brains of individuals with DS from early development until early postnatal life. The results of the experimental work conducted in this thesis suggest a critical loss of physiologic phosphorylation of tau at several neurodegeneration-related sites on the protein including Thr-181, Thr-212, Ser-214, Ser-202/Thr-205, and Thr-231 in individuals with DS. This outcome was noted primarily in the rhombencephalic structures, and to minor extent in rostral brain areas (the hippocampus and the internal capsule). With exception of the subiculum, total amount of tau did not differ between groups. Thus, this data strongly suggest functional tau disturbance, as shown by region-specific selective loss of tau phosphorylation in DS brains during development. The results show that tau could be another principal player in the pathophysiology of cognitive impairment in DS and a further link to AD.

    Item Type: Thesis (MSc thesis)
    Keywords: Tau, Alzheimer’s disease, neurodegeneration, development, phosphorylation
    Number of Pages: 61
    Language of Content: English
    Mentor / Comentors:
    Mentor / ComentorsIDFunction
    dr. Gabor G. KovacsMentor
    dr. Ivan MilenkovićComentor
    Link to COBISS: http://www.cobiss.si/scripts/cobiss?command=search&base=50126&select=(ID=11317065)
    Institution: University of Ljubljana
    Department: Faculty of Education
    Item ID: 4109
    Date Deposited: 16 Nov 2016 10:24
    Last Modified: 16 Nov 2016 10:24
    URI: http://pefprints.pef.uni-lj.si/id/eprint/4109

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