On methodology and appropriate inference regarding possible genetic factors in typical, late-onset AD

Diagnosis of AD in both probands and relatives, and its typically late onset, pose difficulties for the interpretation of its apparent familial aggregation-a possible indicator of genetic causes. Recent methodologic improvements have ameliorated these difficulties somewhat, and new studies incorporating these improvements suggest much greater familial risk in AD than has been previously reported. Actual risk to aged relatives remains a topic of controversy, and the true role of genetic factors in the etiology of AD will probably require the application of the classical genetic methods of twin and linkage studies.