Alzheimer hastalığının tanısında ve yayılımında nöron kökenli ekzozomlar

Alzheimer's Disease (AD) is the most widespread neurodegenerative disease seen in elderly population over the world. Since the lack of definitive diagnosis, treatment, and also clear understanding of its pathogenesis; AD is very interesting and challenging topic to search. Exosomes are the smallest class of extracellular vesicles that are nano-sized and secreted from every cell type including central nervous system cells. Exosomes contain nucleic acids, proteins, pathogens, etc. as cargo molecules and they carry them to recipient cells in their environment. Since they have exosome-specific proteins in their membranes, exosomes can be separated from body fluids and disease-specific molecular alterations in exosomes can be determined. In this thesis, neuron-derived exosomes (NDE) were isolated from plasma samples of AD patients and healthy individuals. Dysregulated miRNAs in those exosomes were determined by small-RNA sequencing. 10 miRNAs were determined as dysregulated and validation of the most dysregulated miRNA, hsa-let-7e-5p, was performed by qRT-PCR to demonstrate its biomarker potential in NDEs of AD patients. Also, human microglial cells were treated with NDEs of patients which contain high level of upregulated hsa-let-7e-5p and miR-96-5p in order to examine their role in cell-to-cell interaction by affecting cytokine levels at protein level and gene expression of IL-1β, IL-6, TNF-α were determined via ELISA and qRT-PCR methods. Results showed that certain miRNAs were altered in NDEs of AD patients and validation of them may confirm their biomarker potential. Also, exosomal miRNAs may be involved in cell-to-cell interactions.