The present invention relates to methods and compositions for modulating levels of amyloid-&bgr； peptide (A&bgr；) exhibited by non-neuronal (i.e., peripheral) cells, fluids, or tissues. The invention also relates to modulation of A&bgr； levels via selective modulation (e.g., inhibition) of &gamma；-secretase activity. The invention also relates to methods of preventing, treating or ameliorating the symptoms of a disorder, including but not limited to an A&bgr；-related disorder, by administering a compound that result in the modulation of &gamma；-secretase in a non-neuronal tissue, either directly or indirectly to prevent, treat or ameliorate the symptoms of a brain A&bgr； disorder, such as Alzheimer's disease.
