Mutant presenilin 2 transgenic mice: A large increase in the levels of Aβ342 is presumably associated with the low density membrane domain that contains decreased levels of glycerophospholipids and sphingomyelin

Naoya Sawamura, Maho Morishima-Kawashima, Hatsue Waki, Kimio Kobayashi, Takashi Kuramochi, Matthew P. Frosch, Kai Ding, Mamoru Ito, Tae Wan Kim, Rudolph E. Tanzi, Fumitaka Oyama, Takeshi Tabira, Susumu Ando, Yasuo Ihara

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Abstract

The N141I mutation in presenilin (PS) 2 is tightly linked with a form of autosomal dominant familial Alzheimer's disease in the Volga German families. We previously reported that mouse brains harboring mutant PS2 contained increased levels of amyloid β protein (Aβ) 42 in the Tris-saline-soluble fraction (Oyama, F., Sawamura, N., Kobayashi, K., Morishima-Kawashima, M., Kuramochi, T., Ito, M., Tomita, T., Maruyama, K., Saido, T. C., Iwatsubo, T., Capell, A., Walter, J., Grinberg, J., Ueyama, Y., Haass, C. and Ihara, Y. (1998) J. Neurochem. 71, 313-322). Here, using a new extraction protocol, we quantitated the A/β40 and Aβ42 levels in the Tris-saline-insoluble fraction. The insoluble Aβ levels were found to be higher than the soluble Aβ levels, and the insoluble Aβ42 levels were markedly increased in mutant PS2 transgenic mice. To investigate the origin of the insoluble Aβ42, we prepared the detergent-insoluble, low density membrane fraction. This fraction from two independent lines of mutant PS2 transgenic mice contained remarkably increased levels of Aβ42 and significantly low levels of glycerophospholipids and sphingomyelin. This unexpected finding suggests that a large increase in the levels of Aβ42 in mutant PS2 mice is presumably induced through alterations of the lipid composition in the low density membrane domain in the brain.

Original languageEnglish
Pages (from-to)27901-27908
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number36
DOIs
Publication statusPublished - 2000 Sep 8
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Sawamura, N., Morishima-Kawashima, M., Waki, H., Kobayashi, K., Kuramochi, T., Frosch, M. P., Ding, K., Ito, M., Kim, T. W., Tanzi, R. E., Oyama, F., Tabira, T., Ando, S., & Ihara, Y. (2000). Mutant presenilin 2 transgenic mice: A large increase in the levels of Aβ342 is presumably associated with the low density membrane domain that contains decreased levels of glycerophospholipids and sphingomyelin. Journal of Biological Chemistry, 275(36), 27901-27908. https://doi.org/10.1074/jbc.M004308200