Aβ25-35 induces rapid lysis of red blood cells: Contrast with aβ1-42 and examination of underlying mechanisms

Mark P. Mattson, James G. Begley, Robert J. Mark, Katsutoshi Furukawa

Research output: Contribution to journalArticle

Abstract

Amyloid β-peptide (Aβ) is produced by many different cell types and circulates in blood and cerebrospinal fluid in a soluble form. In Alzheimer's disease (AD), Aβ forms insoluble fibrillar aggregates that accumulate in association with cells of the brain parenchyma and vasculature. Both full- length Aβ (Aβ1-40/42) and the Aβ25-35 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 Aβ1-40/42 and may also be exposed to Aβ aggregates associated with the luminal surfaces of cerebral microvessels. We therefore examined the effects of Aβ25-35 and Aβ- 42 on human red blood cells (RBCs) and report that Aβ25-35, in contrast to Aβ1-42, induces rapid (10-60 min) lysis of RBCs. The mechanism of RBC lysis by Aβ25-35 involved ion channel formation and calcium influx, but did not involve oxidative stress because antioxidants did not prevent cell lysis. In contrast, Aβ1-42 induced a delayed (4-24 h) damage to RBCs which was attenuated by antioxidants. The damaging effects of both Aβ25-35 and Aβ1- 42 towards RBCs were completely prevented by Congo red indicating a requirement for peptide fibril formation. Aβ1-42 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 Aβ1-42 in previously reported alterations in RBCs from AD patients.

Original languageEnglish (US)
Pages (from-to)147-153
Number of pages7
JournalBrain Research
Volume771
Issue number1
DOIs
StatePublished - Oct 10 1997
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Calcium
  • Free radical
  • Ion current
  • Oxidative stress
  • Vascular amyloid

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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