High density lipoprotein decreases beta-amyloid toxicity in cortical cell culture.
A hallmark of Alzheimer's disease (AD) is the extracellular deposition and accumulation of a 39-43 amino peptide, known as the amyloid beta (A beta) protein, within the brain. It has been postulated that A beta may in some way contribute directly to AD pathogenesis. The epsilon 4 allele of apolipoprotein E (apoE) is a major AD risk factor. Since both apoE and A beta are components of lipoproteins in plasma and cerebrospinal fluid, we asked whether lipoproteins and apoE isoforms would modify the toxicity of A beta (1-42) in cortical cell cultures. We show that high density lipoprotein with or without apoE reduces A beta toxicity and that apoE in the absence of lipoproteins does not affect A beta toxicity. These results suggest that interactions between A beta and lipoproteins in the brain could influence AD pathogenesis.
Farhangrazi
Z S
ZS
Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA.
Ying
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Dugan
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Fagan
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Holtzman
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D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D001057:Apolipoproteins E / Q000032:analysis / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D012307:Risk Factors
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL