Mutations in the β-amyloid precursor protein (APP), presenilin-1 and presenilin-2 cause inherited forms of Alzheimer's disease, but how do these protein interact, normally and in the disease process? In 1996, researchers Nazneen Dewji and S. Jonathan Singer, University of California, San Diego (UCSD), predicted that the three proteins participate in specific cell-to-cell binding and chemical signaling between cells involved in normal human growth and development. They also predicted that, as a byproduct of these normal events, processes are set in motion that result in the production of β-amyloid and the eventual development of Alzheimer's disease. In today's issue of the Proceedings of the National Academy of Sciences, Dewji and Singer report evidence showing that, as predicted, β-APP on one cell surface does bind specifically to either PS-1 or PS-2 on a second cell surface. They also report that this cell-to-cell binding results in rapid and characteristic chemical changes inside one or both the cells. These findings, say Dewji and Singer, establish the long-sought functional connection between the β-APP and presenilin proteins. The results lend strong support to the pair's original proposal that such a specific cell-to-cell interaction is a first and necessary stage in the production of the β-amyloid widely believed to promote Alzheimer's disease.—June Kinoshita
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- Dewji NN, Singer SJ. Specific intercellular binding of the beta-amyloid precursor protein to the presenilins induces intercellular signaling: its significance for Alzheimer's disease. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):15055-60. PubMed.