Apolipoprotein E genotype, atherosclerosis, and cognitive decline: the Rotterdam Study.

The apolipoprotein E4 allele (APOE epsilon 4) and atherosclerosis are risk factors for cognitive decline. We investigated whether the effects of APOE epsilon 4 and atherosclerosis on cognitive decline are independent. A population-based follow-up study was performed on 838 subjects who were non-demented at baseline.

Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3.

Genetic linkage studies have indicated that chromosome 14q24.3 harbours a major locus for early-onset (onset age <65 years) Alzheimer's disease (AD3). Positional cloning efforts have identified a novel gene S182 or presenilin 1 as the AD3 gene.

A mutation in codon 717 of the amyloid precursor protein gene in an Australian family with Alzheimer's disease.

DNA from the probands of seven Australian families with hereditary Alzheimer's disease was screened for the presence of known mutations in the amyloid precursor protein (APP) gene on chromosome 21 using single stranded conformational polymorphism (SSCP) analysis [14]. One subject was found to have a mutation causing a Val-->Ile substitution at position 717. This was confirmed by restriction enzyme digestion and sequencing.

The apolipoprotein E epsilon 2 allele is associated with an increased risk of early-onset Alzheimer's disease and a reduced survival.

It was suggested that in contrast to the E4 allele, the E2 allele of the apolipoprotein E gene (APOE*2) has a protective effect for late-onset Alzheimer's disease and early-onset Alzheimer's disease (EOAD). We studied the role of the APOE*2 allele in the pathogenesis of EOAD in a Dutch population-based study of 175 probable EOAD patients with onset age at or before 65 years and 532 age-matched controls. In our population, there was no evidence for a protective effect of the APOE*2 allele on the risk of EOAD.

Immunoreactivity for p53 and mdm2 and the detection of p53 mutations in human malignant mesothelioma.

Previous immunohistochemical studies on malignant mesothelioma with antibodies recognizing both the wild and the mutant types of the p53 protein have shown immunoreactivity in 25-70% of cases. This study was designed to determine whether there is immunoreactivity for p53 and mdm2 protein in malignant mesothelioma and to correlate p53 expression with the detection of mutations in p53 at DNA level. In 10 of 15 cases there was immunoreactivity for p53.