Abstract: Assay-guided affinity fractionation and reverse phase high pressure liquid chromatography (HPLC) methodology to isolate, test and characterize the most active water-soluble ingredients within Cat's Claw, or Uncaria tomentos. These components appear to account for the majority of the amyloid or A&bgr; fibrillogenesis inhibitory activity. Individual fractions and/or compounds as isolated by HPLC are tested in relevant in vitro and/or animal models, and found to consistently demonstrate inhibition of amyloid or A&bgr; fibrillogenesis. Related extraction methods are disclosed.

Abstract: A method of producing antibodies comprising the step of encoding a peptide sequence from a Domain I perlecan splice variant, wherein the peptide sequence is used to produce anti-peptide antibodies.

Abstract: The invention provides a transgenic non-human animal expressing a perlecan encoding transgene. Also provided is a double-transgenic non-human animal expressing a perlecan and an amyloid encoding transgene. A method of screening for a compound which alters the rate or extent of amyloid deposition is additionally provided. The method consists of: (a) constructing a perlecan transgenic animal; (b) administering an effective amount of a test compound to said perlecan transgenic animal; and (c) determining whether said test compound alters the extent or rate of amyloid deposition. Finally, the invention provides a method of screening for a compound which alters the rate or extent of amyloid deposition. The method consists of: (a) constructing a perlecan/amyloid double-transgenic animal; (b) administering an effective amount of a test compound to said perlecan/amyloid double-transgenic animal; and (c) determining whether said test compound alters the extent o rate of amyloid deposition.

Abstract: A method of inhibiting amyloid formation, deposition, accumulation, or persistence, or amyloid protein-amyloid protein interactions, amyloid-proteoglycan interactions, amyloid-PG/GAG interactions and/or amyloid-glycosaminoglycan interactions, and/or dissolving or disrupting pre-formed or pre-deposited amyloid fibrils in Alzheimer's Disease in a mammalian subject. In the method a therapeutically effective amount of plant matter from the genus Uncaria, species tomentosa is administered, preferably from the inner bark or root tissue of Uncaria tomentosa.

Abstract: A method of perlecan isolation (from the EHS tumor) which produces “clean” (i.e. substantially “pure”) perlecan is disclosed. Clean perlecan is thus produced in sufficient quantities for use in a number of different in vitro and in vivo assays. In addition, this isolation method exploits a newly discovered aggregating property of a ˜220 kDa heparan sulfate proteoglycan (HSPG) observed during gel filtration chromatography, which allows it to be effectively separated from non-aggregating perlecan. The method employs specific cation exchange, anion exchange, molecular sieve chromatography and immobilized GAG affinity chromatography. It is demonstrated that there are no other contaminating proteins in the perlecan and HSPG preparations, and that the perlecan core protein is intact. Improved, clean perlecan based, rodent models of fibrillar amyloid protein deposition, accumulation and/or persistence in tissues are disclosed.

Abstract: The invention provides a transgenic non-human animal expressing a perlecan encoding transgene. Also provided is a double-transgenic non-human animal expressing a perlecan and a amyloid encoding transgene. A method of screening for a compound which alters the rate or extent of amyloid deposition is additionally provided. The method consists of: (a) constructing a perlecan transgenic animal; (b) administering an effective amount of a test compound to said perlecan transgenic animal; and (c) determining whether said test compound alters the extent or rate of amyloid deposition. Finally, the invention provides a method of screening for a compound which alters the rate or extent of amyloid deposition. The method consists of: (a) constructing a perlecan/amyloid double-transgenic animal; (b) administering an effective amount of a test compound to said perlecan/amyloid double-transgenic animal; and (c) determining whether said test compound alters the extent or rate of amyloid deposition.

Abstract: A method of treating an amyloid disease, or a disease characterized by &agr;-synuclein or NAC fibrillogenesis, in a mammalian subject. The method includes administering to the mammal a therapeutically effective amount of a various disclosed proanthocyanidins or a proanthocyanidin characterized by disclosed general formulae. A pharmaceutical composition comprising a therapeutically effective amount of a proanthocyanidin and a pharmaceutically acceptable excipient. The therapeutic amount of the proanthocyanidin is selected for efficacy in treating amyloid, &agr;-synuclein or NAC fibrillogenesis in a mammalian subject.

Abstract: A pharmaceutical composition, or pharmaceutical agent for treating A&bgr; amyloidosis in a patient, having at least one selected laminin peptide or fragment thereof from the group AG73 (SEQ ID NO:1), C-16 (SEQ ID NO:2), A-13 (SEQ ID NO:3), HA3G47 (SEQ ID NO:4), HA3G58 (SEQ ID NO:5), HA3G67 (SEQ ID NO:6), HA3G74 (SEQ ID NO:7), HA3G76 (SEQ ID NO:8), HA3G79 (SEQ ID NO:9), HA3G83 (SEQ ID NO:10), A4G82 (SEQ ID NO:11), A5G15 (SEQ ID NO:12), A5G56 (SEQ ID NO:13), A5G80 (SEQ ID NO:14), A5G81 (SEQ ID NO:15), A5G82 (SEQ ID NO: 16), A5G84 (SEQ ID NO:17), A5G101 (SEQ ID NO:18), and A5G109 (SEQ ID NO:19) (Sequence Group A); and a method for enhancing A&bgr; amyloid fibril formation, or of forming amyloid-plaque like deposits in vitro, including incubating A&bgr; 1-40 or A&bgr; 1-42 with a selected laminin-derived polypeptide from the group A-13 (SEQ ID NO:3), HA3G47 (SEQ ID NO:4), HA3G58 (SEQ ID NO:5), HA3G83 (SEQ ID NO:10), LAM-L (SEQ ID NO:20), A4G10 SEQ ID NO:21), A4G46 (SEQ ID NO:22), A4G47 (SEQ ID NO:23), A4G84 (SEQ

Abstract: Assay-guided affinity fractionation and reverse phase high pressure liquid chromatography (HPLC) methodology to isolate, test and characterize the most active water-soluble ingredients within Cat's Claw, or Uncaria tomentos. These components appear to account for the majority of the amyloid or A&bgr; fibrillogenesis inhibitory activity. Individual fractions and/or compounds as isolated by HPLC are tested in relevant in vitro and/or animal models, and found to consistently demonstrate inhibition of amyloid or A&bgr; fibrillogenesis. Related extraction methods are disclosed.

Abstract: Co-incubation of an amyloid protein with sulfated macromolecules as a method for the formation of amyloid plaques. The amyloid protein may be the beta-amyloid protein or the prion protein or the like. Amyoid plaque formation in one embodiment proceeds in vitro and desireably produces amyloid plaques that stain with Congo red and demonstrate a maltese-cross pattern when viewed under polarized light. The method also produces amyloid plaques that demonstrate an “amyloid star” appearance when viewed by transmission electron microscopy.

Abstract: A method for inhibiting the formation or persistence of brain amyloid deposits in a patient, including administering to the patient a therapeutically effective amount of plant matter from a plant of the genus Hypericum, species perforatum.

Abstract: A method for diagnosing an amyloid disease, or a susceptibility to an amyloid disease, in a patient, where the disease is related to the levels of a PTI-HS7 antigen in a sample from the patient. The method includes testing with a PTI-HS7 antibody for elevated levels of PTI-HS7 antigen in the patient, whereby any elevated levels of PTI-HS7 antigen are indicative of the presence, susceptibility to, or progression of, the amyloid disease in the patient.

Abstract: A method of treating an amyloid disease, or a disease characterized by alpha-synuclein or NAC fibrillogenesis, in a mammalian subject. The method includes administering to the mammal a therapeutically effective amount of a various disclosed catechins or green tea extract. A pharmaceutical composition comprising a therapeutically effective amount of a catechin and a pharmaceutically acceptable excipient. The therapeutic amount of the catechin or green tea extract is selected for efficacy in treating amyloid, alpha-synuclein or NAC fibrillogenesis in a mammalian subject.

Abstract: A pharmaceutical agent for treating an amyloid disease in a patient, wherein the pharmaceutical agent comprises a glucose monosaccharide containing at least one anionic group, or a pharmaceutically acceptable salt thereof. The agent is directed to amyloid diseases in general and to Alzheimer's disease in particular. Methods of treating an amyloid disease in a patient by administering therapeutically effective amounts of a glucose monosaccharide containing at least one anionic group are also presented.

Abstract: Laminin and specific laminin-derived protein fragments are disclosed as potent inhibitors of Alzheimer's disease type amyloidoses. A specific region is identified within laminin which interacts with the Alzheimer's disease beta-amyloid protein and contributes to the observed inhibitory and therapeutic effects.

Abstract: An isolated polynucleotide that is a splice variant of perlecan formed by a partial or complete deletion of a number of exons within domain I of perlecan, the number of exons deleted from domain I numbering less than the number of exons in domain I. An isolated polynucleotide that is a splice variant of perlecan formed by an insertion of nucleotides within domain I of perlecan. A method of detection and/or quantitation of a splice variant of perlecan domain I gene in a sample, the method comprising making complimentary DNA (cDNA) from messenger RNA (mRNA) in the sample, amplifying portions of the cDNA corresponding to the perlecan gene or parts thereof and detecting and quantifying the amplified cDNA in order to detect or quantify the splice variant.

Abstract: Green tea and other natural and synthetic sources of catechins, and bioflavanoids, flavanols, flavandiols, flavanoids, and tannins or derivatives thereof, are disclosed for the preparation of a pharmaceutical composition or dietary supplement for the treatment, prevention or management of amyloidosis in a mammalian subject susceptible to, or afflicted by, such a disease. Use of the green tea and its constituents and methods of use are also disclosed.

Abstract: A method for treating brain amyloid deposits and the symptoms and conditions associated with brain amyloid deposits using the plant Uncaria tomentosa and extracts therefrom

Abstract: In vivo assays for selecting candidate therapeutics for inhibiting amyloidoses, such as congophilic and fibrillar &bgr;/A4 amyloid deposition in brain. A candidate reagent is administered to a first rat in a first infusate comprising &bgr;/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 &bgr;/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 &bgr;/A4 peptide and perlecan.

Abstract: A pharmacological agent comprising a therapeutically effective amount of plant matter from a plant of the genus Uncaria, the plant matter and the therapeutic amount of the plant matter selected for efficacy in treating an amyloid disease such as Alzheimer's Disease in a patient. The preferred plant of the genus Uncaria is Uncaria tomentosa, and the preferred plant matter is an extract obtained from the inner bark or root tissue.