Abstract: Methods for treating Alzheimer's Disease (AD) using modulators of lysosomal activity are described herein. More particularly, methods described herein relate to the use and application of compounds or agents that enhance lysosomal activity for the treatment of AD. In a particular aspect, the method relates to the use and application of compounds or agents that increase the pH of the lysosome and/or increase the overall activity of lysosomal proteases for the treatment of AD. Also described herein are methods and assays for screening to identify compounds or agents that increase the pH of the lysosome and/or increase the overall activity of lysosomal proteases for the treatment of AD.

Abstract: Methods for treating Alzheimer's Disease (AD) using modulators of lysosomal activity are described herein. More particularly, methods described herein relate to the use and application of compounds or agents that enhance lysosomal activity for the treatment of AD. In a particular aspect, the method relates to the use and application of compounds or agents that increase the pH of the lysosome and/or increase the overall activity of lysosomal proteases for the treatment of AD. Also described herein are methods and assays for screening to identify compounds or agents that increase the pH of the lysosome and/or increase the overall activity of lysosomal proteases for the treatment of AD.

Abstract: Methods for treating Alzheimer's Disease (AD) using modulators of lysosomal activity are described herein. More particularly, methods described herein relate to the use and application of compounds or agents that enhance lysosomal activity for the treatment of AD. In a particular aspect, the method relates to the use and application of compounds or agents that increase the pH of the lysosome and/or increase the overall activity of lysosomal proteases for the treatment of AD. Also described herein are methods and assays for screening to identify compounds or agents that increase the pH of the lysosome and/or increase the overall activity of lysosomal proteases for the treatment of AD.

Abstract: The invention features methods of diagnosing and treating a patient having Alzheimer's disease or other neuronal atrophy-associated dementia by determining or altering, respectively, the level of activity of pathways from the endoplasmic reticulum to lysosomes in the patient.

Abstract: The invention features methods for identifying compounds useful for the treatment of Alzheimer's disease. The invention also features methods of identifying genes involved in Alzheimer's disease pathology.

Abstract: The present invention describes a dissociated cell culture system comprising cells of the hippocampus, one of the brain areas affected by Alzheimer's Disease (AD) or amyloid beta-related diseases. This culture system comprises hippocampal neuronal and glial cells from animal models of AD, particularly, but not limited to, double transgenic mice expressing both the human APP mutation (K670N:M671L) (mAPP), and the human PS1 mutation (M146L) (mPS1), and serves as a powerful tool for the screening and testing of compounds and substances, e.g., drugs, for their ability to affect, treat, or prevent AD or ?-amyloid-related diseases. The effects of a test substance on the cells in this culture system can be quantitatively assessed to determine if the test substance affects the cells biochemically and/or electrophysiologically, and/or optically, and/or immunocytochemically. The present in vitro culture system is advantageous for AD drug screening, because it is rapid and efficient.

Abstract: The invention features methods for identifying compounds useful for the treatment of Alzheimer's disease.

Abstract: The present invention describes cell-based screening methods that allow for the elimination of false-positive results due to nonspecific toxicity of test compounds, while detecting those compounds that specifically modulate cellular metabolites in metabolic pathways associated with diseases and disorders, with particular regard to Alzheimer's disease. The methods are particularly suited to high-throughput screening techniques to identify compounds (drugs) that are effective in a cell-based system. The methods of the invention involve determining within a cell system the levels of both a metabolic precursor and a metabolite of interest and have broad application in high-throughput drug discovery and identification, particularly for precursor and metabolite molecules which are associated with disease and disease progression, such as Alzheimer's disease.

Abstract: Disclosed is a method of diagnosing Alzheimer's disease in a patient by measuring the level of a lysosomal hydrolase or lysosomal protease inhibitor in the patient's cerebrospinal fluid. The invention also features methods of measuring the progression of the disease and screening therapeutic compositions for treating Alzheimer's disease.

Abstract: The invention provides a method of diagnosing Alzheimer's disease. The method utilizes presenilin-1, whose level is found to be substantially decreased in Alzheimer's patients. Included in the invention are diagnostic kits for Alzheimer's disease and methods of screening for effective therapeutics for the disease. The invention also provides a method of studying the function and regulation of presenilin-1 in brain by the use of primate retinoblastoma cells.

Abstract: Methods for screening individuals for Alzheimer's disease are disclosed. Also disclosed are antibodies that immunochemically react with the isoforms of calcium-activated neutral proteinases which are characteristic of Alzheimer's disease. Also disclosed are methods for screening drugs which are useful in treating or preventing Alzheimer's disease.

Abstract: The invention provides a method of diagnosing Alzheimer's disease in a human patient by measuring the amount of p33 present in a biological sample from a patient who may have Alzheimer's disease relative to the amount of p33 in a control sample from an unaffected human. Also included in the invention are diagnostic kits for Alzheimer's disease and methods of screening for effective therapeutics for Alzheimer's disease.

Abstract: Disclosed is a method of diagnosing Alzheimer's disease in a patient by measuring the level of cathepsin D in the patient's cerebrospinal fluid.

Abstract: This invention is directed to two highly purified neural calcium-activated neutral proteinase (CANP or calpain) inhibitors, known as high molecular weight calpastatin (HMWC) and low molecular weight calpastatin (LMWC). The invention also relates to recombinant DNA molecules which code for, and antibodies which bind to these proteins. The present invention is further directed to the use of these calpastatin proteins.

Abstract: Methods for screening individuals for Alzheimer's disease are disclosed. Also disclosed are antibodies that immunochemically react with the isoforms of calcium-activated neutral proteinases which are characteristic of Alzheimer's disease. Also disclosed are methods for screening drugs which are useful in treating or preventing Alzheimer's disease.

Abstract: This invention is directed to two highly purified neural calcium-activated neutral proteinase (CANP or calpain) inhibitors, known as high molecular weight calpastatin (HMWC) and low molecular weight calpastatin (LMWC). The invention also relates to recombinant DNA molecules which code for, and antibodies which bind to these proteins. The present invention is further directed to the use of these calpastatin proteins.