Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.507526
Title: The genetic analysis and clinical features of early onset familial Alzheimer's disease
Author: Mullan, Michael John
Awarding Body: University of London
Current Institution: Imperial College London
Date of Award: 1993
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Abstract:
This thesis details the genetic analysis and clinico-genetic correlates of early onset familial Alzheimer's disease (AD). Multiply affected families have been examined for linkage to markers on two candidate chromosomes, 21 and 14. The analysis demonstrates linkage between the β amyloid precursor protein (APP) gene and AD in five early onset (< 65 years) families in which three different mutations were subsequently discovered. Simulation studies were used extensively and enabled the evaluation of lod values below the accepted criterion of 3.0 in single families. Clinical details of these families are presented. In general, these families show classical AD symptoms and signs but with additional prominent features previously recognised in early onset disease. Linkage to βAPP is excluded in analyses of other early onset families which are shown to be linked to the long arm of chromosome 14. A comparison of clinical features is made between allelic variants of the βAPP locus and chromosome 14 linked families. In particular, analysis of variance of age of onset in early onset families supports the notion of clinico-genetic heterogeneity by demonstrating family specific ages of onset and correlation between genetic aetiology and age of onset; the very early onset families show collective evidence of linkage to chromosome 14 and the families with mean onset in the 50s have βAPP mutations.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.507526  DOI: Not available
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