Showing papers by "Alison Goate published in 1990"
Harvard University1, Boston University2, National Institutes of Health3, University of Antwerp4, Imperial College London5, University of Toronto6, University of Minnesota7, University of Florence8, University of Turin9, Pierre-and-Marie-Curie University10, University of Massachusetts Medical School11, Mexican Social Security Institute12, University of Brescia13, University of Pavia14, Russian Academy15, Columbia University16, Life Technologies17
TL;DR: The inheritance of five polymorphic DNA markers from the proximal long arm of chromosome 21 in a large unselected series of pedi-grees with familial Alzheimer's disease suggests that Alzheimer's Disease is not a single entity, but rather results from genetic defects on chromosome 21 and from other genetic or nongenetic factors.
Abstract: Alzheimer's disease, a fatal neurodegenerative disorder of unknown aetiology, is usually considered to be a single disorder because of the general uniformity of the disease phenotype. Two recent genetic linkage studies revealed co-segregation of familial Alzheimer disease with the D21S1/S11 and D21S16 loci on chromosome 21. But two other studies, one of predominantly multiplex kindreds with a late age-of-onset, the other of a cadre of kindreds with a unique Volga German ethnic origin, found absence of linkage at least to D21S1/S11. So far it has not been possible to discern whether these conflicting reports reflect aetiological heterogeneity, differences in methods of pedigree selection, effects of confounding variables in the analysis (for example, diagnostic errors, assortative matings), or true non-replication. To resolve this issue, we have now examined the inheritance of five polymorphic DNA markers from the proximal long arm of chromosome 21 in a large unselected series of pedigrees with familial Alzheimer's disease. Our data suggest that Alzheimer's disease is not a single entity, but rather results from genetic defects on chromosome 21 and from other genetic or nongenetic factors.
415 citations
Journal Article•
TL;DR: A physical map spanning 10 megabases of this region of the chromosome is constructed by means of pulsed-field gel electrophoresis and analysis of somatic cell hybrids to establish the order of chromosome 21 loci and identify several CpG-rich sequences close to the four most centromeric loci, suggesting the location of genes in this region.
Abstract: Evidence from linkage studies suggests that familial Alzheimer disease (AD) can be caused by a defect in a gene on the proximal long arm of chromosome 21. We have constructed a physical map spanning 10 megabases of this region of the chromosome by means of pulsed-field gel electrophoresis and analysis of somatic cell hybrids. Our data have allowed us to establish the order of chromosome 21 loci--cen-(S16,S48)-S13-S46-S4-(S52,S110)-(S1,S1 1)--and are thus of immediate relevance both to multipoint linkage analysis in families affected by AD and for moving from this linkage to the isolation of the genetic defect. We have also been able to identify several CpG-rich sequences close to the four most centromeric loci, suggesting the location of genes in this region. These probes, which are all within 1.5 megabases of one another, are currently the markers most tightly linked to the AD locus. Genes identified in this region can therefore be considered as candidates for the disease locus.
31 citations
Journal Article•
TL;DR: If amyloid metabolism is involved in APP and chromosomes 14 and 19 families, it suggests that Alzheimer's disease is a single disease with a common metabolic pathway, however, if other mechanisms are implicated, evidence is provided that dementia is a heterogeneous disorder that shares common clinicopathological features.
Abstract: The discovery of pathogenic mutations in the amyloid precursor protein gene in families with Alzheimer's disease is a major advance in the understanding of the pathogenesis of Alzheimer's disease. In certain families at least, beta-amyloid metabolism plays a central role in the disease process. It is tempting to speculate that beta-amyloid is common to the majority of Alzheimer cases. In the immediate future the discovery of the mutations responsible for the condition in those families that show linkage to chromosomes 14 and 19 will enable it to be established whether beta-amyloid is involved in these pedigrees as well. If amyloid metabolism is involved in APP and chromosomes 14 and 19 families, it suggests that Alzheimer's disease is a single disease with a common metabolic pathway. However, if other mechanisms are implicated, evidence is provided that Alzheimer's disease is a heterogeneous disorder that shares common clinicopathological features.
21 citations