Attenuation of the neurotoxic effect of A beta amyloid peptide by apolipoprotein E.
Alzheimer's disease patients have increased frequency of apolipoprotein E allele c4, suggesting apoE4 is a risk factor determining disease. ApoE binds A beta amyloid peptide with great avidity in vitro and in the neuritic plaque. Potentially, binding of A beta to apolipoprotein E could increase A beta neurotoxicity. However, in hippocampal cultures, 0.1 microM apolipoprotein E eliminated the neurotoxicity of 10 microM A beta. Neuronal rescue was dose-dependent and occurred even after 48 hours exposure to A beta, but was overwhelmed by excess A beta. Thus, interaction between these proteins does not directly increase A beta neurotoxicity, and the role of ApoE in Alzheimer's disease remains to be elucidated.
Whitson
J S
JS
Department of Neurology, Baylor College of Medicine, Houston, Texas 77030.
Mims
M P
MP
Strittmatter
W J
WJ
Yamaki
T
T
Morrisett
J D
JD
Appel
S H
SH
D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D009498:Neurotoxins; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D009498:Neurotoxins