Some Developments in the Genetics of Alzheimer's Disease and Related Disorders

Abstract

Recent evidence suggests that Alzheimer''s disease (AD) may prove to be genetically and aetiologically heterogeneous. Genetic heterogeneity is suggested by linkage of the familial form of the disease to chromosome 21 in some but not all families with early onset and in no families with late onset; and secondly, by the discovery of a mutation in the β-amyloid precursor protein gene on chromosome 21, which is present in only a small minority of early onset families. A role for non-genetic factors is indicated by the high rate of discordance for AD in monozygotic twins. The dementia of boxers which is now reported to be associated with the presence of amorphous amyloid-containing plaques as well as tangles may be the first definite example of non-genetic AD. Case-control studies of AD in which the data have been pooled and re-analysed confirm the importance of genetic factors but also support an independent role for head injury. Apart from the early onset families with autosomal dominant inheritance the pooled data do not suggest that genetic factors are markedly different in the early and late onset cases.