Abstract: The present invention discloses nucleic acid molecules encoding AD4 gene products, expression vectors and host cells suitable for expressing such gene products. Also disclosed are methods for treating, preventing, and diagnosing Alzheimer's Disease.

Abstract: The present invention relates to methods and compositions for preventing the endocytosis and cellular internalization of integral membrane amyloid &bgr;-precursor protein (APP) and its subsequent catabolism by blocking or interfering with the association or binding of APP with members of the low density lipoprotein receptor family.

Abstract: The invention relates to rapid methods for determining formation of A&bgr; amyloid and screening compounds which inhibit formation of A&bgr; amyloid in vitro, as well as kits for carrying out the present methods. Such an agent used in vivo may prevent, ameliorate or reverse the symptoms of Alzheimer's disease and A&bgr; amyloidotic disorders related to Alzheimer's disease, Down's syndrome, and Guamanian amyotrophic lateral sclerosis/Parkinson's dementia complex. The process described in this invention involves the rapid induction of A&bgr; amyloid by a heavy metal cation capable of binding to a polypeptide comprising at least amino acids 6 to 28 of A&bgr;, such as zinc to form amyloid and determination of formation of tinctorial A&bgr; amyloid. Moreover, a method of determining effectiveness of a candidate anti-amyloidotic agent for prevention or treatment of A&bgr; amyloidosis is described which uses cell cultures which express at least a human A&bgr; peptide.

Abstract: The disclosed invention relates to the finding that the A2M-2 deletion mutation, which is a predisposing factor for Alzheimer's Disease, leads to the production of altered &agr;2M RNA transcripts and proteins. Based on this finding, the invention provides for new therapeutic agents for AD, including molecules having A&bgr; and low density lipoprotein receptor-related protein (LRP) binding domains, peptides, nucleic acid molecules, antisense oligonucleotides, and viral vectors for gene therapy. In addition, the invention relates to pharmaceutical compositions containing these therapeutic agents, methods of using these therapeutic agents to combat Alzheimer's Disease, and methods of screening for therapeutic agents that can combat Alzheimer's Disease.

Abstract: The present invention relates, in general, to presenilin 2 proteolytic fragments. In particular, the present invention relates to a purified 20 kDa presenilin 2 C-terminal fragment (PS2-CTF); purified nucleic acid molecules coding for the 20 kDa PS2-CTF protein; cells containing the nucleic acid molecules; non-human organisms containing the nucleic acid molecule; antibodies having specific binding affinity to the 20 kDa PS2-CTF; hybridomas containing the antibodies; methods of detecting 20 kDa PS2-CTF in a sample; diagnostic kits; methods for screening compounds that inhibit proteolytic processing of presenilin 2 in a cell, isolated compounds that inhibit proteolytic processing of presenilin 2 in a cell, and a method of inhibiting apoptotic cell death by preventing proteolytic cleavage of presenilin 2 at a cleavage site which generates a 20 kDa C-terminal fragment.

Abstract: The invention relates to the identification of pharmacological agents to be used in the treatment of Alzheimer's disease and related pathological conditions and compositions for treatment of conditions caused by amyloidosis, A&bgr;-mediated formation of ROS, or both, such as Alzheimer's disease, are disclosed.

Abstract: The invention relates to rapid methods for determining formation of A&bgr; amyloid and screening compounds which inhibit formation of A&bgr; amyloid in vitro, as well as kits for carrying out the present methods. Such an agent used in vivo may prevent, ameliorate or reverse the symptoms of Alzheimer's disease and A&bgr; amyloidotic disorders related to Alzheimer's disease, Down's syndrome, and Guamanian amyotrophic lateral sclerosis/Parkinson's dementia complex. The process described in this invention involves the rapid induction of A&bgr; amyloid by a heavy metal cation capable of binding to a polypeptide comprising at least amino acids 6 to 28 of A&bgr;, such as zinc to form amyloid and determination of formation of tinctorial A&bgr; amyloid. Moreover, a method of determining effectiveness of a candidate anti-amyloidotic agent for prevention or treatment of A&bgr; amyloidosis is described which uses cell cultures which express at least a human A&bgr; peptide.

Abstract: The disclosed invention relates to a diagnostic method for Alzheimer's disease based on genotyping the Alpha-2-Macroglobulin locus. A statistically significant correlation was found between inheritance of particular alleles of the Alpha-2-Macroglobulin gene and the occurrence of Alzheimer's disease. The diagnostic method involves the isolation of nucleic acid from an individual and subsequent genotyping by means such as sequencing or restriction fragment length polymorphism analysis. The invention also provides a means of genotype analysis through protein isotyping Alpha-2-Macroglobulin variant proteins. Finally, kits for nucleic acid analysis or protein analysis are taught.

Abstract: The invention relates to the identification of clioquinol as a pharmaceutically therapeutic agent for treatment of Alzheimer's disease and related pathological conditions.

Abstract: The invention relates to a method of identifying an agent useful in treatment of a neurodegenerative disease by assaying for capacitative calcium entry in cells treated with the agent. The invention also relates to a method of identifying an agent which inhibits capacitative calcium entry-linked &ggr;-secretase activity by assaying for capacitative calcium entry in cells treated with the agent. The invention is further related to a method of treatment of a neurodegenerative disease by administering an agent which is capable of potentiating capacitative calcium entry activity.

Abstract: The disclosed invention relates to a diagnostic method for Alzheimer's disease based on genotyping the Alpha-2-Macroglobulin locus. A statistically significant correlation was found between inheritance of particular alleles of the Alpha-2-Macroglobulin gene and the occurrence of Alzheimer's disease. The diagnostic method involves the isolation of nucleic acid from an individual and subsequent genotyping by means such as sequencing or restriction fragment length polymorphism analysis. The invention also provides a means of genotype analysis through protein isotyping Alpha-2-Macroglobulin variant proteins. Finally, kits for nucleic acid analysis or protein analysis are taught.

Abstract: The invention relates to the identification of pharmacological agents to be used in the treatment of Alzheimer's disease and related pathological conditions and compositions for treatment of conditions caused by amyloidosis, A&bgr;-mediated formation of ROS, or both, such as Alzheimer's disease.

Abstract: The present invention broadly relates to the treatment, diagnosis, and prophylactic prevention of Alzheimer's disease. More specifically, the present invention relates to methods and compositions for preventing the endocytosis and cellular internalization of integral membrane amyloid .beta.-precursor protein (APP) and its subsequent catabolism by blocking or interfering with the association or binding of APP with members of the low density lipoprotein receptor family.

Abstract: This invention provides an isolated, vertebrate nucleic acid molecule encoding the normal protein that prevents development of Wilson's disease. This invention also provides a nucleic acid molecule comprising a nucleic acid molecule of at least 15 nucleotides capable of specifically hybridizing with a sequence included within the sequence of the above-described nucleic acid molecule. Finally, this invention provides various uses of the isolated Wilson's disease gene.

Abstract: The disclosed invention relates to assays for detecting and quantifying A.beta. peptide, using solid supports that are coated with heavy metal cations, such as zinc (II) or copper (II) form of a nitriloacetic acid. Further, diagnostic kits are described which are used to carry out the assays of the present invention. An improvement in an assay for detection of A.beta. peptide is suggested which comprises forming a heavy metal cation/solid support complex. The preferred heavy metal cations for this improvement are zinc (II) or copper (II) form of a nitriloacetic acid. Finally, methods and kits for bulk purification of A.beta. peptides from biological fluids are taught.

Abstract: The application concerns methods for modulating transcription from the amyloid .beta.-protein precursor (APP) promoter. The upstream stimulatory factor (USF) is described as being capable of activating transcription from the APP promoter. Also described are USF binding compounds which are capable of down-regulating expression from the APP promoter. Preferred USF binding compounds are the amyloid precursor-like proteins APLP1 and APLP2. The application further concerns a screening assay for determining which candidate USF binding compounds are capable of causing down-regulation of transcription from the APP promoter.

Abstract: This invention provides an isolated, vertebrate nucleic acid molecule encoding the normal protein that prevents development of Wilson's disease. This invention also provides a nucleic acid molecule comprising a nucleic acid molecule of at least 15 nucleotides capable of specifically hybridizing with a sequence included within the sequence of the above-described nucleic acid molecule. Finally, this invention provides various uses of the isolated Wilson's disease gene.