Differential effect of APOE genotype on amyloid load and glucose metabolism in AD dementia
Abstract
OBJECTIVE: To examine the relationships between apolipoprotein E (APOE) ε4 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 ε4 negative, 40 heterozygous, and 22 homozygous Alzheimer disease dementia patients underwent dynamic (90 minutes) [(11)C]Pittsburgh compound B (PIB) and static [(18)F]fluorodeoxyglucose (FDG) PET scans. Parametric nondisplaceable binding potential images of [(11)C]PIB and standardized uptake value ratio images of [(18)F]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 ε4 dose on distributions of both [(11)C]PIB (p for trend <0.05) and [(18)F]FDG (p for trend <0.01). More specifically, a univariate general linear model of individual regions showed increased [(11)C]PIB binding in frontal cortex of APOE ε4 noncarriers compared with APOE ε4 carriers (p < 0.05). In contrast, APOE ε4 carriers had reduced [(18)F]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 ε4 dose effect for amyloid deposition in the frontal lobe, whereas APOE ε4 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.
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Brain metabolic changes can be influenced by APOE genetic variation.
“These changes in brain metabolism can be influenced by APOE genetic variation [12][13][14] .”
From APOE4-drives brain bioenergetic shifts independent of Alzheimer’s disease pathology (2026) · cites this paper as [13]
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- Authors
- Ossenkoppele, R., van der Flier, W. M., Zwan, M. D., Adriaanse, S. F., Boellaard, R., Windhorst, A. D., Barkhof, F., Lammertsma, A. A., Scheltens, P., & van Berckel, B. N. M.
- Affiliations
- Vrije Universiteit Amsterdam (NL)
- From the Department of Neurology & Alzheimer Center (R.O., W.M.v.d.F., M.D.Z., S.F.A., P.S.), Department of Nuclear Medicine & PET Research (R.O., M.D.Z., S.F.A., R.B., A.D.W., A.A.L., B.N.M.v.B.), and Departments of Epidemiology & Biostatistics (W.M.v.d.F.) and Radiology (F.B.), VU University Medical Center, Amsterdam, the Netherlands.
- ORCID
- Venue
- Neurology
- Published
- 2013-01-22
- Volume
- 80
- Issue
- 4
- Pages
- 359-365
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2168873176
- Cited by
- 112
- References
- 6
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 2 · 2023: 6 · 2022: 7 · 2021: 9 · 2020: 16 · 2019: 5 · 2018: 13 · 2017: 5 · 2016: 6 · 2015: 13 · 2014: 12 · 2013: 6
- FWCI
- 7.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- APOE ε4, APOE genotype, amyloid plaques, glucose metabolism, Pittsburgh compound B PET, FDG-PET, binding potential, frontal cortex, occipital cortex, posterior cingulate cortex, dose-dependent effects
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Amyloidosis, Aniline Compounds, Apolipoproteins E, Blood Glucose, Cerebral Cortex, Female, Genotype, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Severity of Illness Index, Thiazoles, Fluorodeoxyglucose F18, Positron-Emission Tomography, Benzothiazoles
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