Abstract: Pharmaceutical compositions comprising a peptidic inhibitor of cathepsin B, such as Z-Arg-Lys-AOMK (Z-R-K-AOMK). Methods for inhibiting neutral pH cathepsin B activity, comprising administering to a subject in need an effective amount of a peptidic inhibitor of cathepsin B. Methods for treatment or prevention of a disease comprising administering to a subject in need an effective amount of a peptidic inhibitor of cathepsin B. Methods of producing pH-selective peptide-AMC substrates and novel peptidic-AOMK inhibitors of cathepsin B.

Abstract: The invention is directed to a method of treating Alzheimer's disease. The method comprises administering a cysteine protease inhibitor to a patient and thereby affecting the disease. In a preferred method, the cysteine protease inhibitor is a cathepsin B inhibitor. A preferred method causes a reversal in the progression of the Alzheimer's disease, especially an improvement in cognitive deficit. A preferred method also causes a reduction in A?. The method includes using a reversible or irreversible cysteine protease inhibitor or a combination thereof.