Methods for monitoring cellular processing of .beta.-amyloid precursor protein
AssigneesAthena Neurosciences, Inc., Eli Lilly and Company
InventorsPeter A. Seubert, Dale B. Schenk, Lawrence C. Fritz
Life of this patent
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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.
Claims26
A method for monitoring the processing of .beta.-amyloid precursor protein (.beta.APP) in cells, said method comprising detecting a soluble .beta.APP fragment secreted from said cells, and a substance which specifically binds to said soluble .beta.APP fragment, wherein the amino acid sequence of said .beta.APP fragment extends substantially from the amino-terminus of .beta.APP to the amino-terminus of .beta.-amyloid peptide (.beta.AP).
A method for determining the presence of a secreted fragment of .beta.-amyloid precursor protein (.beta.APP) in a biological sample, said method comprising:
- exposing the sample to a substance which binds specifically to a C-terminal region on the secreted fragment which comprises an amino-terminal fragment of .beta.APP which results from cleavage of .beta.-amyloid peptide (.beta.AP) from .beta.APP, wherein the amino-terminal fragment extends substantially from the amino-terminus of .beta.APP to the amino-terminus of .beta.AP;
- and
- detecting binding between the substance and the secreted fragment.
A method useful in aiding in the diagnosing or monitoring of Alzheimer's disease in a patient suspected of having Alzheimer's disease, said method comprising:
- measuring in a patient sample the amount of a secreted fragment of .beta.-amyloid precursor protein (.beta.APP), by exposure to a substance which specifically binds to said fragment, wherein the amino acid sequence of said fragment extends substantially from the amino-terminus of .beta.APP to the amino-terminus of .beta.amyloid peptide;
- and
- comparing the measured amount of said fragment with an amount characteristic of normal patients, wherein an elevated amount is an indicator of Alzheimer's disease.
A method for determining the presence of a secreted fragment of .beta.-amyloid precursor protein (.beta.APP) in a biological sample, said method comprising:
- exposing the sample to an antibody which binds specifically to an epitope at the carboxy-terminal end of a fragment of .beta.APP having at its carboxy-terminus, methionine.sup.596, which antibody is substantially free of cross-reactivity with other fragments of .beta.APP having amino acids beyond methionine.sup.596 ;
- and
- detecting binding between the substance and the secreted fragment.
Dependencies are inferred from the claim text.