Heritability for Alzheimer's disease: the study of dementia in Swedish twins.

BACKGROUND

Alzheimer's disease has been thought to have familial and sporadic forms, and several genetic defects have been identified that chiefly explain early-onset familial cases. In this study, our purpose was to detect all cases of dementia in an established twin registry and to estimate total extent of genetic contribution to liability to Alzheimer's disease.

METHODS

At the first stage, members of the registry were screened for dementia, using in-person or telephone mental status testing. At the second stage, those who screened positively and their partners were referred for clinical work-ups, including neuropsychological assessment, physician examination, laboratory tests, and neuroimaging. Clinical diagnoses were assigned at a multidisciplinary consensus conference. Probandwise concordance rates were examined by zygosity, and structural modeling was applied to the data to estimate genetic and environmental influences, using both single- and multiple-threshold models.

RESULTS

Sixty-five pairs were identified in which one or both was demented. The probandwise concordance rate for Alzheimer's disease among monozygotic pairs was 67%; the corresponding figure for dizygotic pairs was 22%. Heritability of liability to Alzheimer's disease was estimated to be .74; to any dementia, .43. The other variance is attributable to environmental influences.

CONCLUSIONS

Findings indicate a substantial genetic effect for these predominantly late-onset Alzheimer's disease cases. At the same time, structural modeling results and large intra-pair differences in age of onset suggest that environmental factors are also important in determining whether and when an individual may develop dementia.