Accelerated Aβ aggregation in the presence of GM1-ganglioside- accumulated synaptosomes of aged apoE4-knock-in mouse brain

Naoki Yamamoto, Urule Igbabvoa, Yukiko Shimada, Yoshiko Ohno-Iwashita, Mariko Kobayashi, W. Gibson Wood, Shinobu C. Fujita, Katsuhiko Yanagisawa

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

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 languageEnglish (US)
Pages (from-to)135-139
Number of pages5
JournalFEBS Letters
Volume569
Issue number1-3
DOIs
StatePublished - 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

Fingerprint

Dive into the research topics of 'Accelerated Aβ aggregation in the presence of GM1-ganglioside- accumulated synaptosomes of aged apoE4-knock-in mouse brain'. Together they form a unique fingerprint.

Cite this