Abeta25-35 induces rapid lysis of red blood cells: contrast with Abeta1-42 and examination of underlying mechanisms.

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.