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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. 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