Methods for Characterizing and Treating Cognitive Impairment In Aging and Disease
First Claim
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1. A method of identifying a gene or a plurality of genes associated with cognitive impairment in a mammal comprising the steps of:
- (a) providing an AI population of aged mammals with cognitive impairment;
(b) providing an AU population of aged mammals without cognitive impairment;
(c) providing a Y population of young mammals;
(d) determining the abundance of a plurality of expressed gene products in one or more of the CA1, CA3, and DG hippocampal tissue of each mammal in the AI, AU and Y populations; and
(e) selecting a gene or a plurality of genes based on a significant increase or decrease in the relative abundance of the gene'"'"'s expressed gene product in the AI population of mammals relative to the combined AU and Y populations or in the AU population of mammals relative to the combined AI and Y populations.
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Abstract
This invention provides methods for identifying genes associated with cognitive impairment and for identifying compounds useful in the treatment of cognitive impairment. The methods can in particular be used to identify genes associated with, and compounds useful in treating, cognitive impairment in aging.
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Citations
44 Claims
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1. A method of identifying a gene or a plurality of genes associated with cognitive impairment in a mammal comprising the steps of:
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(a) providing an AI population of aged mammals with cognitive impairment; (b) providing an AU population of aged mammals without cognitive impairment; (c) providing a Y population of young mammals; (d) determining the abundance of a plurality of expressed gene products in one or more of the CA1, CA3, and DG hippocampal tissue of each mammal in the AI, AU and Y populations; and (e) selecting a gene or a plurality of genes based on a significant increase or decrease in the relative abundance of the gene'"'"'s expressed gene product in the AI population of mammals relative to the combined AU and Y populations or in the AU population of mammals relative to the combined AI and Y populations. - View Dependent Claims (3, 4, 5, 6, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 39)
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2. A method of identifying a gene or a plurality of genes associated with cognitive impairment in a mammal comprising the steps of:
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(a) providing an AI population of aged mammals with cognitive impairment; (b) providing an AU population of aged mammals without cognitive impairment; (c) providing a Y population of young mammals; (d) determining the abundance of a plurality of expressed gene products in one or more of the CA1, CA3, and DG hippocampal tissue of each mammal in the AI, AU and Y populations; (e) selecting a gene or a plurality of genes based on a significant increase or decrease in the relative abundance of the gene'"'"'s expressed gene product in the AI population of mammals relative to the combined AU and Y populations or in the AU population of mammals relative to the combined AI and Y populations; (f) correlating the increased or decreased abundance of a selected gene'"'"'s expressed gene products with the level of cognitive impairment in each mammal of the AU and AI populations; and (g) selecting a gene or a plurality of genes based on a significant correlation between the relative abundance of the gene'"'"'s expressed gene product and the level of cognitive impairment in the mammals. - View Dependent Claims (7, 8, 38)
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40. A method for treating cognitive impairment in a mammal in need of such treatment, the method comprising the step of treating the mammal with GABA-5 α
- 5 receptor agonist.
- View Dependent Claims (41, 42)
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43. A pharmaceutical composition for treating cognitive impairment, the composition comprising pharmaceutically effective amount of a GABA-5 α
- 5 receptor agonist and a pharmaceutically acceptable carrier.
- View Dependent Claims (44)
Specification