Early detection of Alzheimer disease 11C-PiB PET in twins discordant for cognitive impairment

Objective: The aim of this study was to investigate whether cognitively preserved monozygotic or dizygotic cotwins of persons with Alzheimer disease (AD) exhibit increased brain amyloid accumulation. Methods: We performed a cross-sectional carbon-11 labeled 2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (C-11)-Pittsburgh compound B (PiB) PET study on 9 monozygotic and 8 dizygotic twin pairs discordant for cognitive impairment as well as on 9 healthy elderly control subjects. C-11-PiB uptake was analyzed with Statistical Parametric Mapping and with region of interest analysis with the region-to-cerebellum ratio as a measure of tracer uptake. Results: Cognitively preserved monozygotic cotwins of cognitively impaired probands had increased cortical C-11-PiB uptake (117%-121% of control mean) in their temporal and parietal cortices and the posterior cingulate. Cognitively preserved dizygotic subjects did not differ from the controls. Further, the cognitively preserved monozygotic subjects showed similar C-11-PiB uptake patterns as their cognitively impaired cotwins. The cognitively impaired subjects (monozygotic and dizygotic individuals combined) showed typical Alzheimer-like patterns of C-11-PiB uptake. Conclusions: Genetic factors appear to influence the development of Alzheimer-like beta-amyloid plaque pathology. The dissociation between cognitive impairment and brain beta-amyloidosis in monozygotic twins implies that there may be important environmental/acquired factors that modulate the relationship between brain amyloidosis and neurodegeneration. AD may be detectable in high-risk individuals in its presymptomatic stage with C-11-PiB PET, but clinical follow-up will be needed to confirm this. Neurology (R) 2011;77:453-460