Genetic risk factors in familial Alzheimer's disease

In the last 10 years significant progress has been made to describe and ide ntify the underlying biological mechanisms that cause the different manifes tation of Alzheimer's disease. Since the first report of a possible locus o n chromosome 21 in a small group of families with early onset familial Alzh eimer's disease (FAD), considerable progress has been made. Results from li nkage analysis and gene sequencing has provided evidence that a minority of early onset FAD families develops the disease as a result of mutations in the gene coding for the A beta -amyloid precursor protein, and that mutatio ns in presenilin 1 and 2 genes account for a larger subgroup of early onset families. Several other early onset FAD families are clearly not linked to any of these loci, suggesting that other genetic risk factors may exist. R ecent genome-wide scanning studies have revealed the existence of a new loc us on chromosome 12, which, together with inheritance of the epsilon4 allel e of apolipoprotein E gene, on chromosome 19, represent the most important genetic factors associated with an increased risk of developing the disease in late onset FAD families. (C) 2001 Elsevier Science Ireland Ltd. All rig hts reserved.