University of California

William E Van Nostrand

Steven L Wagner

Dennis D Cunningham

Monoclonal antibody and the hybridoma producing the antibody are disclosed. The antibody is produced against an epitope on native secreted forms of .beta.APP. A characteristic of the antibody is that the antibody specifically binds to at least one protein in culture medium in which neuroblastoma cells have been grown. This protein co-migrates in non-reducing polyacrylamide gel electrophoresis with PN-2 isolated from human fibroblast cultures. Other characteristics of the antibody are that the antibody specifically binds to PN-2 and to the secreted form of .beta.APP lacking the Kunitz-type inhibitor domain, the antibody selectively binds to neuritic plaques, and the antibody is sufficiently sensitive to detect secreted forms of .beta.APP in CSF, down to a total concentration of the secreted forms of .beta.APP of 3.75 .mu.g/ml or lower.

Monoclonal antibody produced against native .beta.amyloid precursor

A method of diagnosing a disease with cerebrovascular deposition of amyloid, including Alzheimer's disease, hereditary cerebral hemorrhage with amyloidosis-Dutch type and other amyloidoses, in a mammal is disclosed in which a sample of cerebrospinal fluid is obtained, the level of immunoreactivity toward a monoclonal antibody raised against native PN-2/.beta.APP or other amyloid precursor protein in the sample is measured, and this measured level is compared to the level of immunoreactivity toward this antibody in a sample from

Method of diagnosis of amyloidoses

Immunopurification of Protease Nexin-2 and .beta. amyloid precursor protein is disclosed. Methods of detecting Protease Nexin-2 and the use of these methods in the diagnosis of Alzheimer's disease and other conditions are also disclosed. Additionally, pharmaceutical preparations including Protease Nexin-2 or modified forms thereof are disclosed. Medical uses for the pharmaceutical preparations are also disclosed. These uses include the treatment and prevention of amyloid plaques in Alzheimer's disease and Down's Syndrome

Purification, detection and methods of use of protease Nexin-2

Monoclonal antibodies having a specificity for protease nexin-1 are described. Preferably an antibody has specificity to the reactive protease-binding site. The antibody is used in the affinity purification of PN-1 to produce large quantities of substantially pure PN-1, free of other biologically active molecules. Over a 2000-fold purification of a crude preparation of PN-1 may be obtained. The affinity-purified PN-1 is suitable for use in pharmacological preparations used in the treatment of neurological disease associated with serine protease-mediated inhibition of regenerative processes.

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Irvine, CA, United States of America

William E Van Nostrand