Abstract: Soluble .beta.-amyloid peptide (.beta.AP) is measured in biological fluids at very low concentrations, typically in the range from 0.1 ng/ml to 10 ng/ml. The measurement of .beta.AP concentrations in animals or conditioned medium from cultured cells can be used for drug screening, where test compounds are administered to the animals or exposed to the cultured cells and the accumulation of .beta.AP in the animal or culture medium observed. It has been found that elevated levels of .beta.AP in body fluids, such as blood and cerebrospinal fluid, is associated with the presence of a .beta.AP-related condition in a patient, such as Alzheimer's Disease. Methods for diagnosing and monitoring .beta.AP-related conditions comprise measuring the levels of .beta.AP in such body fluids from a patient.

Abstract: The invention relates to protein or polypeptide compositions capable of inhibiting leukocyte adhesion to, and transmigration across endothelial tissue. The invention further relates to nucleic acid molecules encoding such peptides, pharmaceutical compositions containing such peptides and methods of using such polypeptides.

Abstract: Methods of treating Parkinson's disease in a human by administering an effective amount of at least one monoamine oxidase (MAO) A inhibitor by a nasal, intrapulmonary or parenteral routes are disclosed. Reversible or irreversible MAO A inhibitors, or non-selective MAO inhibitors, can be used, and more than one MAO A inhibitor can be administered concurrently. The MAO A inhibitor can be administered in conjunction with other drugs, such as MAO B inhibitors.

Abstract: Soluble .beta.-amyloid peptide (.beta.AP) is measured in biological fluids at very low concentrations, typically in the range from 0.1 ng/ml to 10 ng/ml. The measurement of .beta.AP concentrations in animals or conditioned medium from cultured cells can be used for drug screening, where test compounds are administered to the animals or exposed to the cultured cells and the accumulation of .beta.AP in the animal or culture medium observed. It has been found that elevated levels of .beta.AP in body fluids, such as blood and cerebrospinal fluid, is associated with the presence of a .beta.AP-related condition in a patient, such as Alzheimer's Disease. Methods for diagnosing and monitoring .beta.AP-related conditions comprise measuring the levels of .beta.AP in such body fluids from a patient.

Abstract: Compositions comprising a novel protease capable of cleaving .beta.-amyloid precursor protein on the amino-terminal side of the .beta.-amyloid peptide therein are provided. The protease is designated .beta.-secretase. The .beta.-secretase may be used in screening assays to identify .beta.-secretase inhibitors, or the .beta.-secretase is combined with a suitable polypeptide substrate and cleavage of the substrate determined in the presence and absence of the test substance.

Abstract: The construction of transgenic animal models for testing potential treatments for Alzheimer's disease are described. The models are characterized by a greater similarity to the conditions existing in naturally occurring Alzheimer's disease, based on expression of all three forms of the .beta.-amyloid precursor protein (APP), APP.sub.695, APP.sub.751, and APP.sub.770), as well as various point mutations based on naturally occurring mutations, such as the London and Indiana familial Alzheimer's disease (FAD) mutations at amino acid 717, and predicted mutations in the APP gene. The APP gene constructs are prepared using the naturally occurring promoter, as well as inducible promoters such as the mouse metallothionine promoter, which can be regulated by addition of heavy metals such as zinc to the animal's water or diet, and promoters such as the rat neuron specific enolase promoter, human .beta.

Abstract: Processing of .beta.-amyloid precursor protein (.beta.APP) is monitored by detecting the secretion of a soluble .beta.APP fragment resulting from cleavage of .beta.APP at the amino-terminus of .beta.-amyloid peptide. In vivo monitoring of secretion of the .beta.APP fragment may be monitored for diagnosis and prognosis of Alzheimer's disease and other .beta.-amyloid-related diseases, while in vitro monitoring of such secretion from cultured cells may be monitored to identify inhibitors of .beta.-amyloid production. The .beta.APP fragment may be detected using antibodies and other specific binding substances which recognize a carboxy-terminal residue on the fragment.

Abstract: The invention provides methods and compositions for treating neurodegeneration in mammalian cells by administering a phospholipase A2 inhibitor.

Abstract: The invention provides transgenic non-human animals and transgenic non-human mammalian cells harboring a transgene encoding an APP polypeptide comprising the Swedish mutation.

Abstract: The present invention provides methods for identifying beta amyloid production inhibitors, wherein cells are cultured under conditions which result in secretion of a soluble fragment of beta amyloid precursor protein. The amino acid sequence of the fragment extends from the amino terminus of beta APP to the amino terminus of the beta amyloid peptide. The cultured cells are exposed to test compounds which cause a change in the secreted amount of the soluble fragment of beta APP which is determined.

Abstract: Processing of .beta.-amyloid precursor protein (.beta.APP) is monitored by detecting the secretion of a soluble amino-terminal fragment or .beta.APP (ATF-.beta.APP) resulting from cleavage of .beta.APP at the amino-terminus of .beta.-amyloid peptide. Secretion of ATF-.beta.APP in animal models may be monitored to identify inhibitors of .beta.-amyloid production. The ATF-.beta.APP may be detected using antibodies and other specific binding substances which recognize a carboxy terminal residue on the fragment. Animals expressing the Swedish mutation of .beta.APP are described which produce abundant amounts of ATF-.beta.APP.

Abstract: A nucleic acid construct is described which when expressed in cells, results in the production of APP695, APP751 and APP770. The construct is the cDNA for APP770 with the genomic sequences encoding the KI and OX-2 regions substituting for those regions present in the cDNA.

Abstract: Soluble .beta.-amyloid peptide (.beta.AP) is measured in biological fluids at very low concentrations, typically in the range from 0.1 ng/ml to 10 ng/ml. The measurement of .beta.AP concentrations in animals or conditioned medium from cultured cells can be used for drug screening, where test compounds are administered to the animals or exposed to the cultured cells and the accumulation of .beta.AP in the animal or culture medium observed. It has been found that elevated levels of .beta.AP in body fluids, such as blood and cerebrospinal fluid, is associated with the presence of a .beta.AP-related condition in a patient, such as Alzheimer's Disease. Methods for diagnosing and monitoring .beta.AP-related conditions comprise measuring the levels of .beta.AP in such body fluids from a patient.

Abstract: Intracellular free calcium concentrations are lowered by administering certain dihydropyridine derivatives to cells. Dihydropyridine and other test compounds are screened for their ability to lower intracellular free calcium, particularly by inhibiting the influx of calcium through calcium leak channels, and the identified compounds incorporated into pharmaceutical compositions. Exemplary dihydropyridine derivative compounds include 4-(3-trifluoromethylphenyl)-2,6-dimethyl-3,5-dicarbomethoxy-1,4-dihydropyr idine; 4-(4-bromophenyl)-2,6-dimethyl-3,5-dicarbomethoxy-1,4-dihydropyridine; 4-(4-trifluoromethylphenyl)-2,6-dimethyl-3,5-dicarbomethoxy-1,4-dihydropyr idine; 4-(4-methylphenyl)-2,6-dimethyl-3,5-dicarbomethoxy-1,4-dihydropyridine; and 4-(4-cyanophenyl)-2,6-dimethyl-3,5-dicarbomethoxy-1,4-dihydropyridine.

Abstract: A method for identifying compounds capable of inhibiting the production of .beta.-amyloid peptide in cells comprises exposing cultured cells in one or more test compounds. The cells are cultured under conditions which produce amyloid precursor protein and which result in intracellular accumulation of an approximately 22 kD polypeptide which includes the entire sequence of the .beta.-amyloid peptide. Test compounds which cause a change in the accumulation of the 22 kD polypeptide are considered likely candidates for use as drugs for treating .beta.-amyloid diseases, such as Alzheimer's disease.

Abstract: This invention provides a rectally administered composition for inhibiting epileptic seizure and to its methods of use. The composition contains, in a suitable solvent, an anti-epileptic agent for inhibiting epileptic seizure, a buffer for maintaining pH, and a thickener for imparting a viscosity to the composition effective for rectal administration by injection to a patient in epileptic seizure.

Abstract: Processing of .beta.-amyloid precursor protein (.beta.APP) is monitored by detecting the secretion of a soluble .beta.APP fragment resulting from cleavage of .beta.APP at the amino-terminus of .beta.-amyloid peptide. In vivo monitoring of secretion of the .beta.APP fragment may be monitored for diagnosis and prognosis of Alzheimer's disease and other .beta.-amyloid-related diseases, while in vitro monitoring of such secretion from cultured cells may be monitored to identify inhibitors of .beta.-amyloid production. The .beta.APP fragment may be detected using antibodies and other specific binding substances which recognize a carboxy-terminal residue on the fragment.

Abstract: A proteolytic enzyme isolated from human tissue which exhibits a proteolytic activity to hydrolyze Met-Asp peptide bond in an amyloid-like substrate is disclosed. This enzyme has been designated "amyloidin" because it proteolytically cleaves a Met-Asp bond similar to the one present in the amyloid precursor protein to release a fragment having the mature Asp terminus of the .beta.-amyloid peptide. Antibodies to the amyloidin protease are also provided. Methods to isolate and purify the amyloidin protease are provided, as well as assays to screen for inhibitors of the amyloidin protease. Also disclosed is the gene encoding the protease and methods for expression of the protease by recombinant DNA means.

Abstract: The present invention is related generally to methods and compositions for identifying and quantitating particular .alpha.1-antichymotrypsin species in a biological sample. More particularly, the present invention is related to methods and compositions for detecting and measuring a brain .alpha.1-antichymotrypsin species that is produced in brain tissue of individuals having a neuropathological condition and which is detectable in accessible biological samples. The invention provides detection assays, such as sandwich binding assays, for detecting and quantitating brain .alpha.1-antichymotrypsin in a biological sample, such as blood, urine, cerebrospinal fluid, or tissue. These detection assays are useful for detecting and diagnosing neuropathological diseases and for identifying cells of a human central nervous system lineage, and for other medical applications. The invention also provides binding components, such as antibodies that bind to brain .alpha.

Abstract: A proteolytic enzyme isolated from human tissue which exhibits a proteolytic activity to hydrolyze Met-Asp peptide bond in an amyloid-like substrate is disclosed. This enzyme has been designated "amyloidin" because it proteolytically cleaves a Met-Asp bond similar to the one present in the amyloid precursor protein to release a fragment having the mature Asp terminus of the .beta.-amyloid peptide. Antibodies to the amyloidin protease are also provided. Methods to isolate and purify the amyloidin protease are provided, as well as assays to screen for inhibitors of the amyloidin protease. Also disclosed is the gene encoding the protease and methods for expression of the protease by recombinant DNA means.