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However, the effect of CLA on the generation of neurotoxic amyloid\u2010\u03b2 (A\u03b2) protein remains unclear. We found that c9,t11 CLA significantly suppressed the generation of A\u03b2 in mouse neurons. CLA treatment did not affect the level of \u03b2\u2010site APP\u2010cleaving enzyme 1 (BACE1), a component of active \u03b3\u2010secretase complex presenilin 1 amino\u2010terminal fragment, or A\u03b2 protein precursor (APP) in cultured neurons. BACE1 and \u03b3\u2010secretase activities were not directly affected by c9,t11 CLA. Localization of BACE1 and APP in early endosomes increased in neurons treated with c9,t11 CLA; concomitantly, the localization of both proteins was reduced in late endosomes, the predominant site of APP cleavage by BACE1. The level of CLA\u2010containing phosphatidylcholine (CLA\u2010PC) increased dramatically in neurons incubated with CLA. Incorporation of phospholipids containing c9,t11 CLA, but not t10,c12 CLA, into the membrane may affect the localization of some membrane\u2010associated proteins in intracellular membrane compartments. Thus, in neurons treated with c9,t11 CLA, reduced colocalization of APP with BACE1 in late endosomes may decrease APP cleavage by BACE1 and subsequent A\u03b2 generation. Our findings suggest that the accumulation of c9,t11 CLA\u2010PC\/LPC in neuronal membranes suppresses the production of neurotoxic A\u03b2 in neurons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15490-fig-0008-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  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