Abstract
Aging and apolipoprotein E4 (apoE4) expression are strong risk factors for the development of Alzheimer's disease (AD); however, their pathological roles remain to be clarified. In the process of AD development, the conversion of the nontoxic amyloid β-protein (Aβ) monomer to its toxic aggregates is a fundamental process. We previously hypothesized that Aβ aggregation is accelerated through the generation of GM1 ganglioside (GM1)-bound Aβ which acts as a seed for Aβ fibril formation. Here we report that GM1 level in detergent-resistant membrane microdomains (DRMs) of synaptosomes increased with age and that this increase was significantly pronounced in the apoE4- than the apoE3-knock-in mouse brain. Furthermore, we show that Aβ aggregation is markedly accelerated in the presence of the synaptosomes of the aged apoE4-knock-in mouse brain. These observations suggest that aging and apoE4 expression cooperatively accelerate Aβ aggregation in the brain through an increase in the level of GM1 in neuronal membranes.
Original language | English (US) |
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Pages (from-to) | 135-139 |
Number of pages | 5 |
Journal | FEBS Letters |
Volume | 569 |
Issue number | 1-3 |
DOIs | |
State | Published - Jul 2 2004 |
Bibliographical note
Funding Information:This study was supported by Grants-in-Aid for Scientific Research on Priority Area (C)-Advanced Brain Science Project from the Ministry of Education, Culture, Sports, Science and Technology and the Organization for Pharmaceutical Safety and Research of Japan, and grant (1P0AG-18357) from the National Institutes of Health, USA.
Keywords
- Alzheimer's disease
- Amyloid β-protein
- Apolipoprotein E
- Ganglioside
- Lipid raft