Sporadic Alzheimer's disease (AD) is a multifactorial disease to which both genetic and environmental factors contribute. Therefore twin pairs are useful in studying its pathogenesis and etiology. Cerebral glucose metabolism has been found to be reduced in AD patients. We studied cerebral glucose metabolism in seven monozygotic (MZ) and nine same-sexed dizygotic (DZ) twin pairs discordant for AD using positron emission tomography. To obtain objective and explorative results concerning differences in glucose metabolism, the analysis was made utilizing modern voxel-based analysis methodology statistical parametric mapping and automated region-of-interest analysis. In the demented MZ and DZ co-twins cerebral glucose metabolism was extensively reduced compared to controls. The non-demented MZ co-twins showed reduced metabolism in inferior frontal, lateral temporal, parietal and medial temporal cortices as well as in the thalamus, putamen and right amygdala. In contrast, no reductions were found in the non-demented DZ co-twins. The reduction found in the non-demented MZ co-twins may be an indicator of genetic susceptibility to AD.