The cerebral formation of Amyloid β（Aβ） is a critical pathological feature of Alzheimer＇s disease（AD）.An accumulation of this peptide as senile plaques（SP） was already reported by Alois Alzheimer,the discover...The cerebral formation of Amyloid β（Aβ） is a critical pathological feature of Alzheimer＇s disease（AD）.An accumulation of this peptide as senile plaques（SP） was already reported by Alois Alzheimer,the discoverer of the disease.Yet the exact contribution of Aβ to AD development remains elusive.Moreover,while extensive cerebral Aβ formation leads to fibril formation in many species,AD-like symptoms apparently depend on the highly conserved N-terminal residues R5,Y10 and H13.The amino acids were also shown to lead to the formation of Aβ-heme complexes,which exhibit peroxidase activity in the presence of H_2O_2.Taking together these observations we propose that the formation and enzymatic activity of the named complexes may represent an essential aspect of AD pathology.Furthermore,Aβ is also known to lead to cerebral micro-vessel destruction（CAA） as well as to hemolytic events.Thus we suggest that the Aβ-derived cerebral accumulation of blood-derived free heme represents a likely precondition for the subsequent formation of Aβ-heme complexes.展开更多
基金supported by the Alzheimer Forschung Initiative e.V.(AFI 13810)
文摘The cerebral formation of Amyloid β（Aβ） is a critical pathological feature of Alzheimer＇s disease（AD）.An accumulation of this peptide as senile plaques（SP） was already reported by Alois Alzheimer,the discoverer of the disease.Yet the exact contribution of Aβ to AD development remains elusive.Moreover,while extensive cerebral Aβ formation leads to fibril formation in many species,AD-like symptoms apparently depend on the highly conserved N-terminal residues R5,Y10 and H13.The amino acids were also shown to lead to the formation of Aβ-heme complexes,which exhibit peroxidase activity in the presence of H_2O_2.Taking together these observations we propose that the formation and enzymatic activity of the named complexes may represent an essential aspect of AD pathology.Furthermore,Aβ is also known to lead to cerebral micro-vessel destruction（CAA） as well as to hemolytic events.Thus we suggest that the Aβ-derived cerebral accumulation of blood-derived free heme represents a likely precondition for the subsequent formation of Aβ-heme complexes.
