Haneda E, Ishii K, Sakata M, Oda K, Toyohara J, Ishiwata K, Senda M, Ito K, Kuwano R, Iwatsubo T.
Influence of APOE2 Genotype on Global and Regional Amyloid Deposition.Human Amyloid Imaging Abstract.
2012 Jan 1;
Apolipoprotein E (APOE) e2 allele has been implicated in reduced risk for Alzheimer’s disease (AD). However, the details of APOE2 role are mostly unknown. In this study, we evaluated the influence of APOE2 on the global and the regional brain accumulation of1C-Pittsburgh compound B (PiB) in three nation-wide prospective imaging studies of AD; Alzheimer’s Disease Neuroimaging Initiative (US-ADNI), Austrarian Imaging Biomarker and Lifestyle (AIBL), and Japanese Alzheimer’s Disease Neuroimaging Initiative (J-ADNI).
We analyzed the baseline1C-PiB scan data acquired0-70 min post-injection in all the studies. The PET images were coregistered to individual MRI data, and automated VOI analysis were performed using DARTEL template, standard set of volumes of interest, and cerebrospinal fluid volume correction. The regional (precuneus, frontal, temporal and parietal cortices) uptake was evaluated in reference to that of the cerebellum. The mean cortical uptake (mcSUVR) was regarded as the representative value of individual global cortical amyloid deposition. The cut-off mcSUVR value for PiB-positivity was set at.5 for all the studies. Among all the studies, the number of subjects in each APOE genotype with PiB positive or negative (PiB+/PiB-) were; e2e2 (0/1), e2e3 (4/20), e2e4 (7/3), e3e3 (71/106), e3e4 (110/31) and e4e4 (14/19).
In the PiB-positive subjects,1C-PiB uptake level in e2e4 genotype was significantly lower in mean cortical area (17.5%, p<0.01) and precuneus (17.1%, p<0.005) relative to those in e4e4 genotype. In contrast, no significant difference was observed in other regions (frontal, temporal and parietal) between the groups of e2-positive and e2-negative genotype.
These results suggest the possibility that ApoE e2 allele might be implicated in the suppression of AD risk via the inhibition of amyloid deposition in the brain especially in precuneus.