Murine synaptosomal lipid raft protein and lipid composition are altered by expression of human apoE 3 and 4 and by increasing age
Abstract
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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The serum lipidomic similarity between APOE4hAβ and APOE3hAβ rats mirrors the lipid homogeneity observed in synaptosomes isolated from 2-month-old mice expressing human APOE3 and APOE4.
“This serum lipidomic similarity between APOE4hAβ and APOE3hAβ rats mirrors the lipid homogeneity observed in synaptosomes isolated from 2-month-old mice expressing human APOE3 and APOE4 [87].”
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- 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.
- Affiliations
- University of Minnesota (US)
- Goethe University Frankfurt (DE)
- Corresponding author
- Wood, W.G.
- Venue
- Journal of the Neurological Sciences
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 229-230
- Pages
- 225-232
- ISSN
- 0022-510X (ISSN-L)
- OpenAlex
- W2120324354
- Cited by
- 41
- References
- 48
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 3
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the Neurological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (1P0AG-18357)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein E, APOE ε4, APOE3, Alzheimer's disease risk factors, lipid rafts, synaptosomes, synaptic plasma membrane, cholesterol distribution, sphingomyelin, flotillin-1, alkaline phosphatase, aging
- MeSH terms
- Aging, Alkaline Phosphatase, Animals, Apolipoproteins E, Cholesterol, Humans, Light, Membrane Proteins, Mice, Transgenic, Scattering, Radiation, Sphingomyelins, Synaptosomes, Glycosylphosphatidylinositols, Membrane Microdomains, Mice, Apolipoprotein E3, Apolipoprotein E4, In Vitro Techniques
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