Screening compounds for the ability to alter the production of amyloid-beta peptide (x-41)
AssigneeAthena Neurosciences, Inc. a Delaware corporation
InventorsMartin Citron, Dennis J. Selkoe, Peter A. Seubert, Dale B. Schenk
Life of this patent
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Abstract
This invention provides methods of screening compounds for their ability to alter the production of Aβ(x≧41) alone or in combination with Aβ(x≦40). The methods involve administering compounds to cells, specifically measuring the amounts of Aβ(x≦40) and Aβ(x≧41) produced by the cells, and comparing these amounts to that produced by the cells without administration of the compounds.
Claims58
A method for determining whether a compound alters the amount of at least one Aβ(x-≧41) peptide produced by a cell, comprising the steps of:
- administering the compound to a culture comprising the cell;
- measuring the amount of the Aβ(x-≧41) peptide, specifically, in a sample from the culture;
- and
- determining whether the measured amount is different than the amount expected in a sample from a culture comprising the cell to which no compound has been administered;
- whereby a difference between the measured amount and the expected amount indicates that the compound alters the amount of an Aβ(x-≧41) peptide produced by the cell.
A method for determining whether a compound alters the amount of at least one Aβ(x-≧41) peptide produced by a cell and alters the amount of either total Aβ or at least one Aβ(x-≦40) peptide produced by the cell comprising:
- administering the compound to a culture comprising the cell;
- measuring the amount of the Aβ(x-≧41) peptide, specifically, in a sample from the culture;
- measuring the amount of total Aβ or the Aβ(x-≦40) peptide, specifically, in a sample from the culture;
- and
- determining whether the measured amounts are different than the amounts expected in a sample from a culture comprising the cell to which no compound has been administered;
- whereby differences between the measured amounts and the expected amounts indicate that the compound alters the amount of the Aβ(x-≧41) peptide by a cell and/or the amount of total Aβ or the Aβ(x-≦40) peptide by the cell.
A kit for specifically detecting at least one Aβ(x-≧41) peptide and at least one Aβ(x-≦40) peptide in a sample comprising:
- a binding substance specific for at least one Aβ(x-≧41) peptide;
- and
- a binding substance specific for at least one Aβ(x-≦40) peptide.
A kit for specifically detecting at least one Aβ(x-≧41) peptide and either total Aβ or at least one Aβ(x-≦40) peptide in a sample in a sandwich immunoassay comprising:
- a) at least two different binding substances for measuring the amount of Aβ(x-≧41) peptide;
- and
- b) at least two different binding substances for measuring the amount of total Aβ or Aβ(x-≦40) peptides.
A method for determining whether a compound alters the amount of at least one Aβ(x-≧41) peptide produced by a non-human mammal and alters the amount of either total Aβ or at least one Aβ(x-≦40) peptide produced by the non-human mammal comprising:
- measuring a first amount of the Aβ(x-≧41) peptide in a sample from a non-human animal used as a model of Alzheimer's disease;
- measuring a first amount of total Aβ or the Aβ(x-≦40) peptide in a sample from the non-human animal;
- administering the compound to the non-human animal;
- measuring a second amount of the Aβ(x-≧41) peptide in a sample from the non-human animal;
- measuring a second amount of total Aβ or the Aβ(x-≦40) peptide in a sample from the non-human animal;
- and
- comparing the first amounts with the second amounts,
- whereby the comparison indicates whether the compound increases, decreases, or leaves unchanged the amount of the Aβ(x-≧41) peptide and increases, decreases, or leaves unchanged the amount of the Aβ(x-≦40) peptide.
Dependencies are inferred from the claim text.