Potentiation of β-amyloid polymerisation by low-density lipoprotein enhances the peptide's vasoactivity
Alzheimer's disease (AD) is characterised by the accumulation of insoluble β-amyloid (Aβ) fibrils in the brain. Factors that promote Aβ fibrillogenesis may influence the pathogenesis of AD and represent targets for therapeutic intervention. Some Aβ deposited in AD may originate in the circulati...
Saved in:
Published in | Biochimica et biophysica acta Vol. 1670; no. 2; pp. 147 - 155 |
---|---|
Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier B.V
22.01.2004
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Alzheimer's disease (AD) is characterised by the accumulation of insoluble β-amyloid (Aβ) fibrils in the brain. Factors that promote Aβ fibrillogenesis may influence the pathogenesis of AD and represent targets for therapeutic intervention. Some Aβ deposited in AD may originate in the circulation and plasma factors could promote Aβ deposition, particularly in the cerebrovasculature. We investigated the effects of plasma low-density lipoprotein (LDL), in both its native and oxidised forms, on Aβ
1–40 fibrillogenesis and vasoactivity. LDL enhanced Aβ fibrillogenesis in a process dependent on LDL concentration and the oxidative state of the lipoprotein, as indicated by measurements of thiobarbituric acid reactive substances (TBARS) and conjugated dienes. LDL's actions were inhibited by the iAβ5 peptide, suggesting that LDL-induced Aβ polymerisation involved β-pleated sheet formation. Potentiated Aβ polymerisation was reflected by enhanced Aβ-mediated vascular responses. Human endothelial cells exposed to fibrillar Aβ generated with LDL, especially oxidised LDL, exhibited decreased 20S proteasome activity. Rat aortic ring constriction induced by noradrenaline was enhanced by Aβ fibrils generated with LDL, with oxidised LDL producing the more marked effects. Should plasma lipoproteins prove to play a role in cerebral Aβ deposition their modification with statins or antioxidants may offer therapeutic benefit. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0304-4165 0006-3002 1872-8006 |
DOI: | 10.1016/j.bbagen.2003.11.005 |