SEARCH FOR THE GENES RESPONSIBLE FOR FAMILIAL ALZHEIMERS-DISEASE

Inherited or Familial Alzheimer's Disease (PAD) has clearly been shown to be a genetically heterogeneous disorder. Mutations in the gene on chromosome 21 encoding the beta-amyloid protein precursor (APP) have been shown to be linked to 2-3% of FAD kindreds examined around the world. A late onset FAD locus has been mapped to a region of chromosome 19 in which a recently isolated APP-like gene, APLPI has also been localized, making this gene a strong candidate to harbor a late-onset FAD defect. More recently, a major FAD locus has been mapped to the long arm of chromosome 14. The chromosome 14 locus appears to be mainly linked to the gene defect in early onset FAD pedigrees. Besides the FAD loci on chromosome 21, 19, and 14, at least two other loci must exist since the gene defect in some early- and late-onset PAD pedigrees do not appear to segregate with markers from any of these autosomes. As different gene defects responsible for various forms of FAD are discovered, perhaps, a common basis for the etiology of this devastating disorder can be discerned.