A large body of evidence suggests that an increase in the brain b-amyloid (Ab) burden contributes to the etiology of Alzheimer's disease (AD). Much is now known about the intracellular processes regulating the production of Ab, however, less is known regarding its secretion from cells. We now report that p-glycoprotein (p-gp), an ATP-binding cassette (ABC) transporter, is an Ab ef¯ux pump. Pharmacological blockade of p-gp rapidly decrease extracellular levels of Ab secretion. In vitro binding studies showed that addition of synthetic human Ab1±40 and Ab1±42 peptides to hamster mdr1-enriched vesicles labeled with the¯uorophore MIANS resulted in saturable quenching, suggesting that both peptides interact directly with the transporter. Finally, we were able to directly measure transport of Ab peptides across the plasma membranes of p-gp enriched vesicles, and showed that this phenomenon was both ATP-and p-gp-dependent. Taken together, our study suggests a novel mechanism of Ab detachment from cellular membranes, and represents an obvious route towards identi®cation of such a mechanism in the brain.

Neuromarketing is upon us. Companies are springing up to offer their clients brain-based information about consumer preferences, purporting to bypass focus groups and other marketing research techniques on the premise that directly peering into a consumer's brain while viewing products or brands is a much better predictor of consumer behavior. These technologies raise a range of ethical issues, which fall into two major categories:(1) protection of various parties who may be harmed or exploited by the research, marketing, and deployment of neuromarketing and (2) protection of consumer autonomy if neuromarketing reaches a critical level of effectiveness. The former is straightforward. The latter may or may not be problematic depending upon whether the technology can be considered to so effectively manipulate consumer behavior such that consumers are not able to be aware of the subversion. We call this phenomenon stealth neuromarketing. Academics and companies using neuromarketing techniques should adopt a code of ethics, which we propose here, to ensure beneficent and non-harmful use of the technology in consideration of both categories of ethics concerns.

Multiple lines of evidence suggest that increased production and/or deposition of the ␤-amyloid peptide, derived from the amyloid precursor protein, contributes to Alzheimer's disease. A growing list of neurotransmitters, growth factors, cytokines, and hormones have been shown to regulate amyloid precursor protein processing. Although traditionally thought to be mediated by activation of protein kinase C, recent data have implicated other signaling mechanisms in the regulation of this process. Moreover, novel mechanisms of regulation involving cholesterol-, apolipoprotein E-, and stress-activated pathways have been identified. As the phenotypic changes associated with Alzheimer's disease encompass many of these signaling systems, it is relevant to determine how altered cell signaling may be contributing to increasing brain amyloid burden. We review the myriad ways in which first messengers regulate amyloid precursor protein catabolism as well as the signal transduction cascades that give rise to these effects. Key Words: Amyloid precursor protein-␤-Amyloid-Alzheimer's disease-Second messengers.

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