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Abstract
Objective: To examine the relationships between apolipoprotein E (APOE) ɛ4 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 ɛ4 negative, 40 heterozygous, and 22 homozygous Alzheimer disease dementia patients underwent dynamic (90 minutes) [11C]Pittsburgh compound B (PIB) and static [18F]fluorodeoxyglucose (FDG) PET scans. Parametric nondisplaceable binding potential images of [11C]PIB and standardized uptake value ratio images of [18F]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 ɛ4 dose on distributions of both [11C]PIB (p for trend <0.05) and [18F]FDG (p for trend <0.01). More specifically, a univariate general linear model of individual regions showed increased [11C]PIB binding in frontal cortex of APOE ɛ4 noncarriers compared with APOE ɛ4 carriers (p < 0.05). In contrast, APOE ɛ4 carriers had reduced [18F]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 ɛ4 dose effect for amyloid deposition in the frontal lobe, whereas APOE ɛ4 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.
GLOSSARY
- AD=
- Alzheimer disease;
- APOE=
- apolipoprotein E;
- BPND=
- nondisplaceable binding potential;
- FDG=
- fluorodeoxyglucose;
- GLM=
- general linear model;
- MMSE=
- Mini-Mental State Examination;
- PIB=
- Pittsburgh compound B;
- PVE=
- partial volume effect;
- RAVLT=
- Rey Auditory Verbal Learning Test;
- ROI=
- region of interest;
- RPM2=
- receptor parametric mapping;
- SUVr=
- standardized uptake value ratio
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
- Received June 6, 2012.
- Accepted September 10, 2012.
- © 2013 American Academy of Neurology
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