Showing papers by "Alison Goate published in 1993"
TL;DR: The authors will review the progress in understanding the pathogenic implications of the genes mutated in familial early onset AD and the mapping studies to identify additional genes involved in late-onset AD.
Abstract: The part that genetics plays in the origin of Alzheimer's disease (AD) is a complex problem that is only now, in the last few years, beginning to be understood. Progress in the study of the epidemiology of AD, discovery of multiple AD loci, and interpreting how mutations affect and produce the AD phenotype have been the initial keys to unlocking the mysteries of this disease. We now know of the existence of at least three AD loci on chromosomes 14, 19, and 21 and are beginning to understand the role that one of these loci, APP, and its mutations plays in the progression of AD. On future studies using animal modeling and the positional cloning of the other AD loci, a definite model for AD should become evident within the next few years.
109 citations
TL;DR: In all cases, there is complete co-segregation of the APP mutation with early onset AD, providing overwhelming statistical evidence that these mutations are pathogenic.
92 citations
TL;DR: To determine the size of the APP gene and the organization of the exons within human genomic DNA, 11 Yeast Artificial Chromosome (YAC), recombinants containing human APP gene sequences are characterized.
Abstract: Several point mutations within exons 16 and 17 of the amyloid precursor protein (APP) gene have been reported that are associated with Alzheimer's disease in a small number of familial cases. To determine the size of the APP gene and the organization of the exons within human genomic DNA, we have characterized 11 Yeast Artificial Chromosome (YAC), recombinants containing human APP gene sequences. The smallest YAC insert was 125 kb, and the largest was 1.4 Mb. The YACs were screened by polymerase chain reaction amplification of APP exons to determine which of the 18 exons coding for APP770 were present. Four of the YACs (D110G1, D110G6, D110E9, and B142F9) contain all 18 exons and at least part of the promoter. Construction of an overlapping map of the gene with all of the YACs demonstrated that 3 of the 11 YACs were chimeric. The orientation and position of the coding sequence on the map was determined by probing digests of the YAC DNA with exon PCR products and the vector arms. The coding region of the APP gene spans approximately 400 kb of genomic DNA.
16 citations
TL;DR: Genetic linkage data is presented in a large family in which non-specific dementia is inherited as an autosomal dominant trait and a quarter of the genome is excluded as the site of the pathogenic mutation in this family.
Abstract: We present genetic linkage data in a large family in which non-specific dementia is inherited as an autosomal dominant trait. We have analyzed 45 highly polymorphic microsatellite sequences and excluded a quarter of the genome as the site of the pathogenic mutation in this family.
10 citations
TL;DR: It is demonstrated that familial non-specific dementia is a novel genetic dementia, and the mutations known to cause familial prion disease, APP-linked familial Alzheimer's disease and candidate regions for Huntington's disease, other forms of Alzheimer's Disease and motor neuron disease are excluded.
10 citations