The genetics of Alzheimer's disease

Abstract
The genetics of Alzheimer's disease is proving to be complex and controversial. Nature Genetics this month contains a paper from Tanzi's group in Boston suggesting that a common polymorphism of α2macroglobulin is associated with a major increase in the risk of developing late onset Alzheimer's disease.1 The data generated heated debate at the sixth international conference on Alzheimer's disease held in Amsterdam at the end of July. At least 70 other reports on the genetics of Alzheimer's disease were presented, implicating over a dozen other genes or genetic loci.2 So what is our current state of knowledge? Missense mutations in three genes are known to cause autosomal dominant forms of early onset Alzheimer's disease: these are the amyloid precursor protein gene located on chromosome 213 and genes for presenilin 1 and presenilin 2 located on chromosomes 14 and 1, respectively. 4 5Studies on these missense mutations have given strong support to the “amyloid cascade hypothesis” of Alzheimer's disease.6 The amyloid precursor protein …