LINKAGE OF FAMILIAL ALZHEIMER-DISEASE TO CHROMOSOME-14 IN 2 LARGE EARLY-ONSET PEDIGREES - EFFECTS OF MARKER ALLELE FREQUENCIES ON LOD SCORES

Alzheimer disease (AD) is a devastating neurodegenerative disease lead ing to global dementia. In addition to sporadic forms of AD, familial forms (FAD) have been recognized. Mutations in the amyloid precursor p rotein (APP) gene on chromosome (CHR) 21 have been shown to cause earl y-onset AD in a small number of pedigrees. Recently, linkage to marker s on CHR 14 has been established in several early-onset FAD pedigrees. We now report lod scores for CHR 14 markers in two large early-onset FAD pedigrees. Pairwise linkage analysis suggested that in these pedig rees the mutation is tightly linked to the loci D14S43 and D14S53. How ever, assumptions regarding marker allele frequencies had a major and often unpredictable effect on calculated lod scores. Therefore, cautio n needs to be exercised when single pedigrees are analyzed with marker allele frequencies determined from the literature or from a pool of s pouses.