LAMBDA-BETA-25-35 INDUCES RAPID LYSIS OF RED-BLOOD-CELLS - CONTRAST WITH LAMBDA-BETA-1-42 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 beta 1-40/42) and the A beta 25-35 fragment can damage and kill neurons by a mechanism that may inv olve oxidative stress and disruption of calcium homeostasis. Circulati ng blood cells are exposed to soluble A beta 1-30/42 and may also be e xposed to A beta aggregates associated with the luminal surfaces of ce rebral microvessels. We therefore examined the effects of A beta 25-35 and A beta 1-42 on human red blood cells (RBCs) and report that A bet a 25-35, in contrast to A beta 1-42, induces rapid (10-60 min) lysis o f RBCs. The mechanism of RBC lysis by A beta 25-35 involved ion channe l formation and calcium influx, but did not involve oxidative stress b ecause antioxidants did not prevent cell lysis. In contrast, A beta 1- 42 induced a delayed (4-24 h) damage to RBCs which was attenuated by a ntioxidants. The damaging effects of both A beta 25-35 and A beta 1-42 towards RBCs were completely prevented by Congo red indicating a requ irement for peptide fibril formation. A beta 1-42 induced membrane lip id peroxidation in RBC, and basal levels of lipid peroxidation in RBCs from AD patients were significantly greater than in age-matched contr ols, suggesting a possible role for A beta 1-42 in previously reported alterations in RBCs from AD patients. (C) 1997 Elsevier Science B.V.