Abstract: In accordance with the present invention, there are provided formulations of gamma secretase modulators (GSMs) which are suitable for oral delivery and have improved transport properties relative to prior art formulations thereof. Also provided are methods for the preparation of such improved formulations and uses thereof for the delivery of GSMs to subjects in need thereof.

Abstract: In accordance with the present invention, it has been discovered that compounds which modulate the ?-secretase enzyme to make more of the shorter, less toxic and less aggregation-prone A? peptides (such as A?37 and A?38), while making less of the longer and more toxic and aggregation-prone AB peptides (such as AB40 and AB42) are useful as gamma-secretase modulators. In addition, these GSM compounds have further been discovered to have the selective property of modulating the formation of various AB peptides, while not inhibiting the overall activity of the ?-secretase enzyme. Thus, such compounds do not impede other critical functions of the ?-secretase enzyme, such as generating fragments from Notch that appear to control gene expression and cell differentiation. Therefore, in accordance with the present invention, there are provided screening assays useful for determining whether test compounds have GSM activity; accordingly, invention assays facilitate the identification of new gamma-secretase modulators.

Abstract: In accordance with the present invention, it has been discovered that compounds which modulate the ?-secretase enzyme to make more of the shorter, less toxic and less aggregation-prone A? peptides (such as A?37 and A?38), while making less of the longer and more toxic and aggregation-prone AB peptides (such as AB40 and AB42) are useful as gamma-secretase modulators. In addition, these GSM compounds have further been discovered to have the selective property of modulating the formation of various AB peptides, while not inhibiting the overall activity of the ?-secretase enzyme. Thus, such compounds do not impede other critical functions of the ?-secretase enzyme, such as generating fragments from Notch that appear to control gene expression and cell differentiation. Therefore, in accordance with the present invention, there are provided screening assays useful for determining whether test compounds have GSM activity; accordingly, invention assays facilitate the identification of new gamma-secretase modulators.

Abstract: Recombinant cells expressing fluorescence resonance energy transfer reporter polypeptides and cell-based assays for apoptosis; screening assays for identifying and selecting candidate compounds modulating apoptosis.

Abstract: The present invention relates to methods and compositions for preventing the endocytosis and cellular internalization of integral membrane amyloid &bgr;-precursor protein (APP) and its subsequent catabolism by blocking or interfering with the association or binding of APP with members of the low density lipoprotein receptor family.

Abstract: The present invention broadly relates to the treatment, diagnosis, and prophylactic prevention of Alzheimer's disease. More specifically, the present invention relates to methods and compositions for preventing the endocytosis and cellular internalization of integral membrane amyloid .beta.-precursor protein (APP) and its subsequent catabolism by blocking or interfering with the association or binding of APP with members of the low density lipoprotein receptor family.