title: Alzheimer's disease: molecular genetics and transgenic animal models.
abstract: Disease-causing mutations in the amyloid precursor protein (APP) gene have been found on chromosome 21 during the last 2 years in some early onset Alzheimer's disease (AD) families. Genetic evidence shows that other genes than the APP are also involved in the aetiology of AD. Linkage to a loci on chromosome 14 has been found in early onset disease. The identification of APP mutation has led to the realization that APP mismetabolism is a central event in the aetiology and pathogenesis of the disease. Experiments to test this in transgenic mice have so far met with little success. There are many possible explanations for the problems to generate transgenic mice. These include the possibilities that mice are incapable of developing AD for reasons dependent on their APP sequence; and that appropriate regulation of APP gene is required for pathology to develop. Current attempts that seem promising to model the disease pathology are the use of homologous recombination to insert the pathogenic mutation and transfection of YACs into transgenic animals.
authors.affiliation: Department of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Lannfelt
authors.forename: R
authors.initials: R
authors.lastname: Folkesson
authors.forename: A H
authors.initials: AH
authors.lastname: Mohammed
authors.forename: B
authors.initials: B
authors.lastname: Winblad
authors.forename: D
authors.initials: D
authors.lastname: Hellgren
authors.forename: K
authors.initials: K
authors.lastname: Duff
authors.forename: J
authors.initials: J
authors.lastname: Hardy
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002891:Chromosomes, Human, Pair 21; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D008967:Molecular Biology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor