Σημασία των ενδοθηλιακών κυττάρων στη νόσο Αλτσχάιμερ: Μελέτη του ρόλου της ενδοκυττάρωσης του Αβ πεπτιδίου, ως μηχανισμού εκκαθάρισης του αμυλοειδούς.

eimer’s disease (AD) is an age-associated, irreversible neurodegenerative disorder. Α fundamental neuropathological hallmark of this disease is the accumulation of the amyloid-beta (Aβ) peptide in the extracellular space and its aggregation in the brain. Interestingly, critical role for a healthy brain is played by clearance mechanisms of endothelial cells, which traverse the Αβ peptide through the Blood Brain Barrier (BBB), a highly selective semipermeable border. Studies in recent years have shown that endothelial cells remove Aβ by endocytosis, and that impairment of this function is key to AD progression. However, the exact contribution of the distinct individual endocytic routes, as well as the involved molecular mechanisms, are largely unexplored. Thus, our lab has recently initiated a study aiming to identify the unexplored endocytic routes in brain endothelial cells that are responsible for clearance of Aβ produced by neuronal cells, and to identify the relationship between endocytic abnormalities and clinical pathologies of AD. The proposed Master’s Thesis Project will contribute to, 1st, the development of an in vitro co-culture BBB model system using endothelial and neuronal cells derived from established isogenic hiPSCs, and to, 2nd, screening of the distinct endocytic routes to identify their contribution in Aβ clearance. The results of this study will improve our understanding in Aβ clearance mechanisms, thus contributing to novel strategies aiming to reduce the load of Aβ peptide in the brain, thereby preventing or delaying the onset of the disease.