Apolipoprotein E and cholesterol affect neuronal calcium signalling: the possible relationship to beta-amyloid neurotoxicity.
Besides the neurotoxic properties of beta-amyloid (beta A4), apolipoprotein E polymorphism seems to play an important role in the pathogenesis of sporadic Alzheimer's disease (AD). The calcium amplifying effect of beta A25-35 (the neurotoxic sequence of beta A4) in dissociated mouse brain neurons and human lymphocytes was nearly abolished by cholesterol (100-500 mumol/l). This effect may be related to the membrane stabilizing properties of cholesterol which could be confirmed by measurements of membrane fluidity. ApoE did not affect the Ca2+ amplifying effect of beta A25-35, but amplified the neuronal Ca2+ response significantly in a very low concentration (100nmol/l). The findings suggest a possible link between AD pathology and ApoE polymorphism by the calcium amplifying effect of ApoE itself as well as by the modulation of beta A4 neurotoxicity by cholesterol.
Hartmann
H
H
Dept. Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany.
Eckert
A
A
Müller
W E
WE
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001054:Apolipoproteins A / Q000494:pharmacology; D001057:Apolipoproteins E / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology; D005454:Fluorescence Polarization; D066298:In Vitro Techniques; D008560:Membrane Fluidity / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D015398:Signal Transduction
D016229:Amyloid beta-Peptides; D001054:Apolipoproteins A; D001057:Apolipoproteins E; D000431:Ethanol; D011189:Potassium Chloride; D002784:Cholesterol; D002118:Calcium