CANDIDATE GENE FOR THE CHROMOSOME-1 FAMILIAL ALZHEIMERS-DISEASE LOCUS

A candidate gene for the chromosome 1 Alzheimer's disease (AD) locus w as identified (STM2). The predicted amino acid sequence for STM2 is ho mologous to that of the recently cloned chromosome 14 AD gene (S182). A point mutation in STM2, resulting in the substitution of an isoleuci ne for an asparagine (N141I), was identified in affected people from V olga German AD kindreds. This N141I mutation occurs at an amino acid r esidue that is conserved in human S182 and in the mouse S182 homolog. The presence of missense mutations in AD subjects in two highly simila r genes strongly supports the hypothesis that mutations in both are pa thogenic.