Murine synaptosomal lipid raft protein and lipid composition are altered by expression of human apoE 3 and 4 and by increasing age

Murine synaptosomal lipid raft protein and lipid composition are altered by expression of human apoE 3 and 4 and by increasing age

Apolipoprotein E (apoE) 4 and aging are risk factors for Alzheimer's disease (AD). Mice expressing human apoE4 and aged wild-type mice show a similarity in the transbilayer distribution of cholesterol in synaptic plasma membranes (SPMs) but differ markedly compared with apoE3 mice and young mic...

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Published in:Journal of the neurological sciences Vol. 229; pp. 225 - 232
Main Authors: Igbavboa, U., Eckert, G.P., Malo, T.M., Studniski, A.E., Johnson, L.N.A., Yamamoto, N., Kobayashi, M., Fujita, S.C., Appel, T.R., Müller, W.E., Wood, W.G., Yanagisawa, K.
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 15-03-2005
Subjects:
Aging
Aging - metabolism
Alkaline Phosphatase - metabolism
Alzheimer's disease
Animals
Apolipoprotein E
Apolipoprotein E3
Apolipoprotein E4
Apolipoproteins E - metabolism
Cholesterol
Cholesterol - blood
Flotillin
Glycosylphosphatidylinositols - metabolism
Humans
In Vitro Techniques
Light
Lipid rafts
Membrane Microdomains - metabolism
Membrane Proteins - metabolism
Mice
Mice, Transgenic
Scattering, Radiation
Sphingomyelin
Sphingomyelins - blood
Synaptosomes - metabolism
AD
ALP
apoE
Lipid rafts
Cholesterol
Aβ
SPM
Apolipoprotein E
Flotillin
Aging
Sphingomyelin
SM
Alzheimer's disease
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Summary:Apolipoprotein E (apoE) 4 and aging are risk factors for Alzheimer's disease (AD). Mice expressing human apoE4 and aged wild-type mice show a similarity in the transbilayer distribution of cholesterol in synaptic plasma membranes (SPMs) but differ markedly compared with apoE3 mice and young mice. The largest changes in cholesterol distribution were observed in the SPM exofacial leaflet where there was a doubling of cholesterol. Lipid rafts are thought to be associated with the exofacial leaflet, and we proposed that lipid raft protein and lipid composition would be associated with apoE genotype and age. Lipid rafts were isolated from synaptosomes of different age groups (2, 12, 24 months) of mice expressing human apoE3 and apoE4. Lipid raft markers, alkaline phosphatase (ALP), flotillin-1, cholesterol and sphingomyelin (SM) were examined. Lipid rafts of young apoE4 mice were more similar to older mice as compared with young apoE3 mice in reductions in alkaline phosphatase activity and flotillin-1 abundance. Lipid raft cholesterol and sphingomyelin levels were not significantly different between the young apoE3 and apoE4 mice but cholesterol levels of lipid rafts did increase with age in both genotypes. Results of the present study demonstrate that the two risk factors for Alzheimer's disease, apoE4 genotype and increasing age have similar effects on brain lipid raft protein markers and these findings support the notion that the transbilayer distribution of cholesterol is associated with lipid raft function.
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ISSN:0022-510X
1878-5883
DOI:10.1016/j.jns.2004.11.037