title: Considering the vascular hypothesis of Alzheimer's disease: effect of copper associated amyloid on red blood cells.
abstract: The vascular hypothesis of Alzheimer's disease (AD) considers cerebral hypoperfusion as a primary trigger for neuronal dysfunction. We have previously reported that red blood cells (RBCs) bind amyloid, which are the characteristic deposits found in AD brains, and interact with amyloid on the vasculature [1-3]. Oxidative stress triggered by these RBC/amyloid interactions could impair oxygen delivery. Recent literature has implicated copper bound amyloid-β peptide (CuAβ) and the associated production of reactive oxygen species (ROS) as one of the primary factors contributing to AD pathology. In this work, we have investigated CuAβ generated RBC oxidative stress. Aβ(1-40) peptide with a stoichiometric amount of copper bound was produced and compared to the metal-free form of the peptide. Different aggregation states of the peptides were isolated and incubated with RBCs for 15 h. Interestingly, CuAβ stimulated a pronounced increase in red cell oxidative stress as indicated by increased hemoglobin (Hb) oxidation, increased formation of fluorescent heme degradation products, and a decrease in RBC deformability. These findings demonstrate a potential role for CuAβ in promoting vascular oxidative stress leading to impaired cerebral oxygen delivery, which may contribute to neurodegeneration associated with AD.
authors.affiliation: Molecular Dynamics Section, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd. 05B129, Baltimore, MD, 21224, USA.
authors.forename: Heather R
authors.initials: HR
authors.lastname: Lucas
authors.affiliation: Molecular Dynamics Section, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd. 05B129, Baltimore, MD, 21224, USA. rifkindj@mail.nih.gov.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Rifkind
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D010108:Oxyhemoglobins / Q000737:chemistry / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010108:Oxyhemoglobins; D017382:Reactive Oxygen Species; D003300:Copper; D010100:Oxygen