title: Abeta25-35 induces rapid lysis of red blood cells: contrast with Abeta1-42 and examination of underlying mechanisms.
abstract: Amyloid beta-peptide (A beta) is produced by many different cell types and circulates in blood and cerebrospinal fluid in a soluble form. In Alzheimer's disease (AD), A beta forms insoluble fibrillar aggregates that accumulate in association with cells of the brain parenchyma and vasculature. Both full-length A beta (A beta1-40/42) and the A beta25-35 fragment can damage and kill neurons by a mechanism that may involve oxidative stress and disruption of calcium homeostasis. Circulating blood cells are exposed to soluble A beta1-40/42 and may also be exposed to A beta aggregates associated with the luminal surfaces of cerebral microvessels. We therefore examined the effects of A beta25-35 and A beta1-42 on human red blood cells (RBCs) and report that A beta25-35, in contrast to A beta1-42, induces rapid (10-60 min) lysis of RBCs. The mechanism of RBC lysis by A beta25-35 involved ion channel formation and calcium influx, but did not involve oxidative stress because antioxidants did not prevent cell lysis. In contrast, A beta1-42 induced a delayed (4-24 h) damage to RBCs which was attenuated by antioxidants. The damaging effects of both A beta25-35 and A beta1-42 towards RBCs were completely prevented by Congo red indicating a requirement for peptide fibril formation. A beta1-42 induced membrane lipid peroxidation in RBC, and basal levels of lipid peroxidation in RBCs from AD patients were significantly greater than in age-matched controls, suggesting a possible role for A beta1-42 in previously reported alterations in RBCs from AD patients.
authors.affiliation: Sanders-Brown Research Center on Aging and Department of Anatomy & Neurobiology, University of Kentucky, Lexington 40536, USA. mmattson@aging.coa.uky.edu
authors.forename: M P
authors.initials: MP
authors.lastname: Mattson
authors.forename: J G
authors.initials: JG
authors.lastname: Begley
authors.forename: R J
authors.initials: RJ
authors.lastname: Mark
authors.forename: K
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D000328:Adult; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D003224:Congo Red / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008563:Membrane Lipids / Q000097:blood; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D007473:Ion Channels; D008563:Membrane Lipids; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); D003224:Congo Red