A mutation at codon 717 of the beta-amyloid precursor protein gene has been found to cosegregate with familial Alzheimer's disease in a single family. This mutation has been reported in a further five out of approximately 100 families multiply affected by Alzheimer's disease. We have identified another family, F19, in which we have detected linkage between the beta-amyloid precursor protein gene and Alzheimer's disease. Direct sequencing of exon 17 in affected individuals from this family has revealed a base change producing a Val----Gly substitution, also at codon 717. The occurrence of a second allelic variant at codon 717 linked to the Alzheimer's phenotype supports the hypothesis that they are pathogenic mutations.

Several families with an early-onset form of familial Alzheimer's disease have been found to harbour mutations at a specific codon (717) of the gene for the beta-amyloid precursor protein (APP) on chromosome 21. We now report, a novel base mutation in the same exon of the APP gene which co-segregates in one family with presenile dementia and cerebral haemorrhage due to cerebral amyloid angiopathy. The mutation results in the substitution of alanine into glycine at codon 692. These results suggest that the clinically distinct entities, presenile dementia and cerebral amyloid angiopathy, can be caused by the same mutation in the APP gene.

A population-based telephone survey was conducted in Connecticut to determine the social and economic impact of work-related musculoskeletal disorders (WRMSDs). Only 10.6% of cases had filed for workers' compensation. Respondents had spent an average of $489 annually out-of-pocket. Only 21% of individuals who had had medical visits or procedures reported having them paid for by workers' compensation. The WRMSD cases reported much higher levels of difficulty in daily tasks rated by the activities of daily living (ADL) scale, with odds ratios (ORs) ranging from 8.2 (child care) to 35.2 (bathing). The cases were significantly more likely to have moved for financial reasons (OR = 2.41), including having lost a home (OR = 3.44). The cases were also significantly more likely to have lost a car due to finances (OR = 2.45), more likely to have been divorced (OR = 1.91), and less likely to have been promoted (OR = 0.45). The study supports significant externalization of costs for WRMSD out of the workers' compensation system and a substantial social and economic impact on workers.