Chromosome 1 gene and gene products related to Alzheimer's disease
Introduction Alzheimer's disease (AD) is a devastating, neurodegenerative progressive disorder and is a common disease in the elderly and is the predominant cause of dementia in people over 65 years of age. The prevalence of AD is estimated to be as high as 18.7% and 47.2% for the 75-84 year and >=85 year age groups respectively Thus, there is a large affected population in most countries of the world. Clinical symptoms of the disease typically begin with subtle short term memory problems. As the disease progresses, difficulty with memory, language, and orientation worsen to the point of interfering with the ability of the person to function independently. Duration of AD from the first symptoms of memory loss until death is 10 years on average, but may range from 6-8 years to more than 20 years. AD always results in death, often from respiratory-related illness. The present invention relates generally to Alzheimer's disease, and more specifically to methods and compositions for use in diagnosis and treatment of Alzheimer's Disease. Technology description Two causative AD loci and 1 risk-modifying gene have been identified. The present invention provides a novel, previously unidentified locus for AD, methods and compositions for diagnosis and treatment of AD, and further provides other, related advantages. The invention provides isolated nucleic acid molecules encoding an AD4 (also known as STM2) gene product. Within other embodiments, nucleic acid molecules are provided which encode a mutant AD4 gene product that increases the probability of Alzheimer's Disease (in a statistically significant manner). Expression vectors are provided and isolated proteins or polypeptides are also provided comprising an AD4 gene product, as well as AD4 peptides of greater than 12, 13, or 20 amino acids. Within yet another aspect of the present invention, methods of treating or preventing Alzheimer's Disease are provided, comprising the step of administering to a patient a vector containing or expressing a nucleic acid molecule as described above, thereby reducing the likelihood or delaying the onset of Alzheimer's Disease in the patient. Within a related aspect, methods of treating or preventing Alzheimer's Disease are provided, comprising the step of administering to a patient a protein as described above, thereby reducing the likelihood or delaying the onset of Alzheimer's Disease in the patient. Within yet another related aspect, methods are provided for treating or preventing Alzheimer's Disease comprising the step of administering to a patient an antibody specific for an AD4 protein as described above, thereby reducing the likelihood or delaying the onset of Alzheimer's Disease in the patient. Within certain embodiments, the above methods may be accomplished by in vivo administration. Also provided by the present invention are pharmaceutical compositions comprising a nucleic acid molecule, vector, host cell, protein, or antibody as described above, along with a pharmaceutically acceptable carrier or diluent. Within other aspects of the present invention, antibodies are provided which specifically bind to an AD4 protein, or to unique peptides derived from the N-terminal, internal, or carboxy-terminal hydrophilic regions. Assays useful within the context of the present invention include those assays for detecting agonists or antagonists of AD4 protein activity. Other assays are useful for the screening of peptide or organic molecule libraries. Still other assays are useful for the identification and/or isolation of nucleic acid molecules and/or peptides within the present invention, or for diagnosis of a patient with an increased likelihood of contracting AD. Another aspect of the present invention provides probes and primers for detecting the AD4 genes and/or mutants thereof. In one embodiment of this aspect, probes are provided that are capable of specifically hybridizing to RNA or DNA from the AD4 gene. The present invention also provides methods for treating or preventing Alzheimer Disease, comprising the step of administering to a patient a vector (e.g., expression vector, viral vector, or viral particle containing a vector) or nucleic acid molecules alone, as described above, thereby reducing the likelihood or delaying the onset of AD. Therapeutic peptides, peptidomimetics, or small molecules may be used to delay onset of AD, lessen symptoms, or halt or delay progression of the disease. Transgenic animals expressing Alzheimer's disease protein may be used to test candidate therapeutics Business opportunity This technology can be used in the diagnosis of AD, in developing assays, and in developing transgenic animals. This technology also provides methods for treating or preventing AD. Intellectual property position A US patent has issued (6,468,791) and US and worldwide patents are pending.
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