Molecular genetics of Alzheimer's disease

At present it is not clear whether Alzheimer's disease is a single disease, a complex syndrome, or a heterogeneous ill-defined group of disorders. In the last few years significant progress has been made in identifying and describing its different manifestations, as well as the underlying biological mechanisms. Modern molecular biology techniques have provided new insights into possible etiological mechanisms. Linkage analysis and gene sequencing studies have produced evidence of a possible locus on chromosome 21 in a small group of families with early onset familial Alzheimer's disease (FAD). It was shown that another small group of early onset FAD families develops the disease as a result of mutations in the gene coding for the beta-amyloid precursor protein, and that in a larger subgroup of early onset families the disease appears to be caused by an unidentified gene on chromosome 14. Several other early onset FAD families are clearly not linked to any of these loci, suggesting that other abnormal genes, probably on different chromosomes, might be the cause of the disease in these families. Finally, it was recently shown that the epsilon 4 allele of apolipoprotein E (ApoE) gene, which has been mapped to chromosome 19, is associated with an increased risk of developing the disease in late onset FAD families and sporadic cases. These results not only evidence that Alzheimer's disease is a genetically heterogeneous disorder, but also delineate new approaches in the study of the etiological and pathogenetic mechanisms of Alzheimer's disease.