Genetics, Alzheimer's disease and senile dementia

Genetic factors in the aetiology of Alzheimer's disease (AD), are now being intensively investigated. The homogeneity of AD is under investigation. There are a few large kindreds with early onset of AD in whom transmission appears to be typically autosomal dominant, and 65% or more of the remaining cases at any age may have genetic aetiology. Both multifactorial and autosomal dominant inheritance with age-dependent expression have been proposed, but the late onset and death of unaffected relatives from competing causes make it difficult to choose between them. Lifetime risk gives the best estimate of incidence in family studies, but clinical and pathological criteria are not clear enough for confident diagnosis of AD in late old age. A role for external factors is indicated by twin studies, and the role of aluminium is currently under investigation. Molecular genetics promises to resolve many questions. The clinicians' role will be to provide well documented families for interdisciplinary research and to help in clarifying diagnosis in late old age.