Substitutions at Codon 22 of Alzheimer's Aβ Peptide Induce Diverse Conformational Changes and Apoptotic Effects in Human Cerebral Endothelial Cells

摘要: Cerebral amyloid angiopathy is commonly associated with normal aging and Alzheimer's disease it also the principal feature of hereditary cerebral hemorrhage amyloidosis Dutch type, a familial condition to point mutation G C at codon 693 beta (Abeta) precursor protein gene resulting in Glu Gln substitution position 22 Abeta (E22Q). The patients carrying AbetaE22Q variant usually present lobar hemorrhages before 50 years age. A different described several members three Italian kindred who presented recurrent hemorrhagic strokes late life, between 60 70 age, extensive cerebrovascular deposition has been found same 22, this time Lys (E22K). We have compared secondary structure, aggregation, fibrillization properties two Abeta40 variants wild type peptide. Using flow cytometry analysis after staining propidium iodide annexin V, we evaluated cytotoxic effects peptides on human endothelial cells culture. Under conditions tested, E22Q peptide exhibited highest content beta-sheet conformation fastest aggregation/fibrillization properties. induced apoptosis concentration 25 micrometer, whereas E22K mutant had no effect. data suggest that amino acids confer distinct structural appear influence onset aggressiveness rather than phenotype.