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

U. Igbavboa, G. P. Eckert, T. M. Malo, A. E. Studniski, L. N.A. Johnson, N. Yamamoto, M. Kobayashi, S. C. Fujita, T. R. Appel, W. E. Müller, W. Gibson Wood, K. Yanagisawa

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)225-232
Number of pages8
JournalJournal of the Neurological Sciences
StatePublished - Mar 15 2005

Bibliographical note

Funding Information:
This work was supported by grants from the NIH (1P0AG-18357), Grant-in-Aid for Scientific Research on Priority Area (C) from the Japanese Ministry of Education, Culture, Sports, Science and Technology, Ministry of Health and Welfare and the Organization for Pharmaceutical Safety and Research of Japan, NATO (Collaborative Linkage Grants, 976648 and 980136) and the Medical Research Program of the Department of Veterans Affairs.


  • Aging
  • Alzheimer's disease
  • Apolipoprotein E
  • Cholesterol
  • Flotillin
  • Lipid rafts
  • Sphingomyelin


Dive into the research topics of 'Murine synaptosomal lipid raft protein and lipid composition are altered by expression of human apoE 3 and 4 and by increasing age'. Together they form a unique fingerprint.

Cite this