Progression of Cerebral Amyloid Load Is Associated with the Apolipoprotein E ε4 Genotype in Alzheimer's Disease

Background Pittsburgh Compound B ([C-11]PiB) is a specific positron emission tomography (PET) marker of cerebral amyloid deposits Only few data have been published on in vivo longitudinal changes of amyloid load in Alzheimer's disease (AD) patients with conflicting results Therefore, little is known about the factors that influence these changes Methods A group of 24 patients with probable AD diagnosed by combining established clinical criteria with an AD typical pattern in [F-18] fluoro deoxy glucose PET underwent [C-11] PiB PET examinations at baseline and after 24 months The difference of amyloid load between the two examinations and the association with clinical and neurobiological variables was examined with a regions of interest approach and voxel based analyses Results Cerebral [C-11] PiB uptake ratio increased significantly by an annual rate of 3 92% Although the increase occurred in all parts of the neocortex no increase was detected in the archipallium The increase was gene-dose dependent (analysis of variance p = 012) to the number of apolipoprotein E epsilon 4 alleles Progression of dementia symptoms was correlated to the [C-11] PiB increase in numerous regions associated with cognition Conclusions The results of this study indicate that a significant increase of amyloid deposition occurs in patients with AD during a relatively short interval of its clinical course The rate of amyloid aggregation rate is closely associated with the apolipoprotein E genotype which might be important for the evaluation of antiamyloid drug treatment effects The present study further emphasizes the value of amyloid plaque imaging as a marker of disease progression and as a potential surrogate marker to be used in antiamyloid drug trials