Abstract: The invention is directed to a method of selecting an agent that prevents cleavage of an APP substrate by contacting a candidate agent with a &bgr;-secretase complex that encompasses cathepsin B and cathepsin L, in the presence of an APP substrate and under conditions that allow for cleavage of the APP substrate by the &bgr;-secretase complex; and selecting the agent that prevents the cleavage of the APP substrate by the &bgr;-secretase complex. The prevention of A&bgr; peptide formation by an individual results in a reduction amyloid plaques. Thus, the invention provides a method of reducing the severity of a condition characterized by amyloid plaque formation such as Alzheimer's Disease.

Abstract: This invention provides a method of determining the proteolytic activity of the in vivo secretases, particularly the &bgr;-secretease and &ggr;-secretease that produce the A&bgr; peptides found in the plaques of Alzheimer Dementia (AD) patients. The invention also provides methods of isolating such secretases and methods of selecting agents that affect the activity of such secretases for developing drugs to treat or prevent dementia.

Abstract: This invention is directed to a novel &bgr;-secretase that produces the A&bgr; peptide found in Alzheimer's Disease. One &bgr;-secretase is a protein having a molecular weight of about 61, 81 or 88 kDa that cleaves an amyloid precursor protein (APP) substrate. Another is a protease complex having a molecular between about 180 and 200 kDa, which, in one embodiment, contains the 61, 81, and 88 kDa proteins and, in another embodiment, contains proteins having a molecular weight of about 66, 60, 33 and 29 kDa. Another &bgr;-secretase has a molecular weight between about 50 and 90 kDA. The invention is also directed to methods of selecting agents that inhibit A&bgr; peptide production and treating Alzheimer's disease in patients.

Abstract: This invention provides a method of determining the proteolytic activity of the in vivo secretases, particularly the &bgr;-secretease and &ggr;-secretease that produce the A&bgr; peptides found in the plaques of Alzheimer Dementia (AD) patients. The invention also provides methods of isolating such secretases and methods of selecting agents that affect the activity of such secretases for developing drugs to treat or prevent dementia.

Abstract: This invention is directed to a novel &bgr;-secretase that produces the A&bgr; peptide found in Alzheimer's Disease. One &bgr;-secretase is a protein having a molecular weight of about 61, 81 or 88 kDa that cleaves an amyloid precursor protein (APP) substrate. Another is a protease complex having a molecular between about 180 and 200 kDa, which, in one embodiment, contains the 61, 81, and 88 kDa proteins and, in another embodiment, contains proteins having a molecular weight of about 66, 60, 33 and 29 kDa. Another &bgr;-secretase has a molecular weight between about 50 and 90 kDA. The invention is also directed to methods of selecting agents that inhibit A&bgr; peptide production and treating Alzheimer's disease in patients.

Abstract: This invention provides a method of determining the proteolytic activity of the in vivo secretases, particularly the &bgr;-secretase and &ggr;-secretase that produce the A&bgr; peptides found in the plaques of Alzheimer Dementia (AD) patients. The invention also provides methods of isolating such secretases and methods of selecting agents that affect the activity of such secretases for developing drugs to treat or prevent dementia.