CEREBRAL VASCULAR ANGIOPATHY: MOLECULAR MECHANISMS OF ENDOTHELIAL DYSFUNCTION

Different forms of hereditary cerebral amyloid angiopathy, are due to mutations of the gene encoding for amyloid beta precursor protein. Among the known mutations, we would like to study two pathological forms, in particular Dutch and Italian types. Amyloid beta protein present in patients affected by these rare gene defects, accumulates and deposits in cerebral blood vessels, especially in to the endothelium, the tissue lining the bood vessels, inducing their rupture and brain hemorrhagie. Both pathologies are poorly undestood and to date there is no specific therapies. Our aim is to study the activity of mutated amyloid beta protein, responsible for Dutch and Italian forms, on vascular endothelium. Our investigation will gather information on the molecular mechanisms responsible for the damage of vascular endothelium induced by beta amyloid protein, leading to cerebral hemorrhagies. An important objective of this proposal is to indicate therapeutical intervantions for repairing vascular endothelium damage caused by mutated beta amyloid protein.