Differential effect of APOE genotype on amyloid load and glucose metabolism in AD dementia

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Objective: To examine the relationships between apolipoprotein E (APOE) epsilon 4 dose and in vivo distributions of both fibrillary amyloid burden and glucose metabolism in the same Alzheimer disease dementia patients, selected for abnormal amyloid imaging. Methods: Twenty-two APOE epsilon 4 negative, 40 heterozygous, and 22 homozygous Alzheimer disease dementia patients underwent dynamic (90 minutes) [C-11]Pittsburgh compound B (PIB) and static [F-18] fluorodeoxyglucose (FDG) PET scans. Parametric nondisplaceable binding potential images of [C-11]PIB and standardized uptake value ratio images of [F-18]FDG were generated using cerebellar gray matter as reference tissue. Frontal, parietal, temporal, posterior cingulate, and occipital cortices were selected as regions of interest. Results: Multivariate general linear models with adjustment for age, sex, and Mini-Mental State Examination showed main effects of APOE epsilon 4 dose on distributions of both [C-11]PIB (p for trend <0.05) and [F-18]FDG (p for trend <0.01). More specifically, a univariate general linear model of individual regions showed increased [C-11]PIB binding in frontal cortex of APOE epsilon 4 noncarriers compared with APOE epsilon 4 carriers (p <0.05). In contrast, APOE carriers had reduced [F-18]FDG uptake in occipital cortex (p <0.05) and a borderline significant effect in posterior cingulate (p = 0.07) in a dose-dependent manner. Conclusion: We found a reversed APOE epsilon 4 dose effect for amyloid deposition in the frontal lobe, whereas APOE epsilon 4 carriership was associated with more profound metabolic impairment in posterior parts of the cortex. These findings suggest that APOE genotype has a differential effect on the distribution of amyloid plaques and glucose metabolism. This may have important implications for emerging therapies that aim to directly intervene in the disease process. Neurology (R) 2013;80:359-365
Original languageUndefined/Unknown
Pages (from-to)359-365
Issue number4
Publication statusPublished - 2013

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