ANALYSIS OF THE C-FOS GENE ON CHROMOSOME-14 AND THE PROMOTER OF THE AMYLOID PRECURSOR PROTEIN GENE IN FAMILIAL ALZHEIMERS-DISEASE

The c-FOS gene product, a putative transacting transcriptional regulat or of the amyloid precursor protein (APP) gene, is a candidate locus f or the familial Alzheimer's disease (FAD) mutation on chromosome 14 (F AD14). In light of this functional relationship, we investigated the n ucleotide sequence and segregation of c-FOS and the nucleotide sequenc e of the 5' APP promoter. Single-stranded conformational polymorphisms (SSCPs) in the c-FOS gene revealed that c-FOS closely cosegregates wi th the FAD14 gene but does not show allelic association with FAD. A co nservative third-position T-->C mutation was demonstrated in exon 2 (c odon 84) of c-FOS, and a C-->G substitution was detected at -209 bp in the 5' promoter of APP. Neither were unique to FAD and are unlikely t o be pathogenic or secondary modifiers of the FAD phenotype. We conclu de that the c-FOS open reading frame is probably not the site of the F AD14 locus, but we cannot exclude the existence of modifier loci on ch romosome 21.