SummaryThere is increasing evidence for genetic heterogeneity in Alzheimer disease. A longitudinal clinical and imaging study had been established in order to determine whether specific phenotypic profiles are present in aetiologically distinct familial Alzheimer disease (FAD) pedigrees. [18F]fluorodeoxyglucose positron emission tomography has been used in conjunction with statistical parametric mapping to determine the relative distribution of hypometabolism. A parietotemporal deficit has been observed in individuals from both amyloid precursor protein mutation and chromosome 14 linked FAD families. Preliminary data from asymptomatic individuals at risk of FAD shows similar, although a less extensive pattern of deficit.