Rodent models of human amyloidoses
First Claim
1. A method for producing a rodent model of Alzheimer'"'"'s disease comprising a) infusing a proteoglycan, or fragments thereof, in combination with a beta-amyloid protein into brain tissue of a rodent, b) allowing sufficient time for the proteoglycan, or fragments thereof, and the beta-amyloid protein to be co-deposited in the brain tissue, and c) detecting the amyloid deposit in the brain tissue using standard staining techniques for fibrillar amyloid.
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Abstract
In vivo assays for selecting candidate therapeutics for inhibiting amyloidoses, such as congophilic and fibrillar β/A4 amyloid deposition in brain. A candidate reagent is administered to a first rat in a first infusate comprising β/A4 peptide and perlecan by continuous infusion for at least one week into hippocampus. The candidate reagent is selected as a candidate therapeutic for inhibiting congophilic and fibrillar β/A4 amyloid deposition in brain if the first infusate diminishes congo red and thioflavin S staining indicative of amyloid deposition adjacent to the infusion site, as compared with a second rat receiving a second infusate consisting essentially of β/A4 peptide and perlecan.
88 Citations
20 Claims
- 1. A method for producing a rodent model of Alzheimer'"'"'s disease comprising a) infusing a proteoglycan, or fragments thereof, in combination with a beta-amyloid protein into brain tissue of a rodent, b) allowing sufficient time for the proteoglycan, or fragments thereof, and the beta-amyloid protein to be co-deposited in the brain tissue, and c) detecting the amyloid deposit in the brain tissue using standard staining techniques for fibrillar amyloid.
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14. A method for producing a rodent model of Alzheimer'"'"'s disease comprising:
- a) infusing directly into a rodent brain an infusate comprised of a heparan sulfate proteoglycan in combination with a beta-amyloid protein;
b) allowing sufficient time for the heparan sulfate proteoglycan and the beta-amyloid protein to be co-deposited in the rodent brain; and
c) detecting an amyloid deposit in the rodent brain using standard staining techniques for fibrillar amyloid.
- a) infusing directly into a rodent brain an infusate comprised of a heparan sulfate proteoglycan in combination with a beta-amyloid protein;
- 15. An in vivo assay for selecting a candidate therapeutic for inhibiting fibrillar amyloid deposition/persistence in brain, the assay comprising a) administering a candidate reagent by continuous infusion directly into brain tissue of a test rodent, the candidate reagent carried in an infusate comprising an amyloid protein and a proteoglycan, b) selecting the candidate reagent as a candidate therapeutic for inhibiting congophilic and fibrillar amyloid deposition/persistence if the infusate diminishes Congo red or Thioflavin S staining indicative of fibrillar amyloid deposition/persistence in the brain, as compared with a control rodent receiving a control infusate not comprising the candidate reagent.
- 18. An in vivo assay for selecting a candidate therapeutic for causing disruption/dissolution of pre-deposited fibrillar amyloid in brain, the assay comprising a) administering to a test rodent by continuous infusion directly into brain tissue of the rodent, an infusate to cause deposition and persistence of fibrillar amyloid, the infusate comprising an amyloid protein and a proteoglycan, b) allowing sufficient time for the amyloid protein and proteoglycan to form fibrillar amyloid in the brain, c) administering a candidate reagent in a second infusate to the rodent by continuous infusion at an infusion site into brain tissue of the rodent, and d) selecting the candidate reagent as a candidate therapeutic for inhibiting congophilic and fibrillar amyloid deposition/persistence if the second infusate diminishes Congo red or Thioflavin S staining indicative of disruption/dissolution of pre-deposited fibrillar amyloid in the brain, as compared with a control animal receiving a control infusate not comprising the candidate reagent.
Specification