Differential effect of APOE genotype on amyloid load and glucose metabolism in AD dementia
Ossenkoppele R, van der Flier WM, Zwan MD, Adriaanse SF, Boellaard R, Windhorst AD, Barkhof F, Lammertsma AA et al.. Neurology, 2012-12-19
Topic: Amyloid, tau and blood-test diagnosis
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 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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APA 7th
Ossenkoppele, R., van der Flier, W. M., Zwan, M. D., Adriaanse, S. F., Boellaard, R., Windhorst, A. D., et al. (2013). Differential effect of APOE genotype on amyloid load and glucose metabolism in AD dementia. Neurology. https://doi.org/10.1212/wnl.0b013e31827f0889
Vancouver
Ossenkoppele R, van der Flier WM, Zwan MD, Adriaanse SF, Boellaard R, Windhorst AD, et al. Differential effect of APOE genotype on amyloid load and glucose metabolism in AD dementia. Neurology. 2013. doi:10.1212/wnl.0b013e31827f0889. PMID: 23255822.
BibTeX
@article{ossenkoppele2013-23255822,
author = {Ossenkoppele, R. and van der Flier, W. M. and Zwan, M. D. and Adriaanse, S. F. and Boellaard, R. and Windhorst, A. D. and Barkhof, F. and Lammertsma, A. A. and others},
title = {{Differential effect of APOE genotype on amyloid load and glucose metabolism in AD dementia}},
journal = {Neurology},
year = {2013},
doi = {10.1212/wnl.0b013e31827f0889},
pmid = {23255822},
url = {https://doi.org/10.1212/wnl.0b013e31827f0889}
}
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Key findings
- 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).
- These findings suggest that APOE genotype has a differential effect on the distribution of amyloid plaques and glucose metabolism.
Why it matters
In Alzheimer's dementia patients with abnormal amyloid scans, the number of APOE ε4 copies affected where amyloid and reduced brain glucose use showed up: there was a reversed ε4 dose effect for amyloid in the frontal lobe, while carrying ε4 was linked to more severe metabolic impairment in the back of the cortex. The authors say this differential effect of APOE genotype may have important implications for emerging therapies that aim to intervene directly in the disease process.
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Study details
- Evidence strengthLow
How this study scored 45/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2013 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 110 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.3 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 3 / 6 | Cited 6.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 1 / 4 | Cited 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Bart N.M. van Berckel: h-index 73 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Vrije Universiteit Amsterdam: institution h-index 1,014 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23255822) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 45 / 100 | — |
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