Study of beta-Amyloid Peptide (Abeta40) Insertion into Phospholipid Membranes Using Monolayer Technique

S.-R. Ji, Y. Wu, and S.-f. Sui^*

Department of Biological Sciences and Biotechnology, State-Key Laboratory of Biomembranes, Tsinghua University, Beijing 100084, People's Republic of China; fax: +8610-62784768; E-mail: suisf@mail.tsinghua.edu.cn

^* To whom correspondence should be addressed.

Received March 7, 2002; Revision received April 22, 2002

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beta-Amyloid peptide (Abeta), a normal constituent of neuronal and non-neuronal cells, has been proved to be the major component of extracellular plaque of Alzheimer's disease (AD). The interaction of Abeta with lipid membranes may be essential for its neurotoxicity. Our previous study revealed that membrane insertion may provide a possible pathway by which Abeta prevents itself from aggregation and fibril formation. In the present work we studied the membrane insertion of Abeta and the factors that affect its insertion ability using a monolayer approach. The results show that Abeta is surface active and can insert into lipid monolayers. When a high level of cholesterol is present, Abeta40 can insert into the phospholipid mixtures simulating physiological membrane composition. Acidic pH enhances Abeta insertion, while the effect of ionic strength is rather complex. Abeta insertion ability may be ultimately relative to cholesterol-rich domains in the monolayers, which indicates strong interaction between Abeta and cholesterol.

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KEY WORDS:beta-amyloid peptide, monolayer, membrane insertion, cholesterol

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