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Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism
Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, Saunders AM, Hardy J.. Proceedings of the National Academy of Sciences of the United States of America, 2005-06-02
Topic: Brain proteins, microglia and lab models
Patients with Alzheimer's disease (AD) have abnormally low positron emission tomography (PET) measurements of the cerebral metabolic rate for glucose (CMRgl) in regions of the precuneus and the posterior cingulate, parietotemporal, and frontal cortex. Apolipoprotein E (APOE) epsilon4 gene dose (i.e., the number of epsilon4 alleles in a person's APOE genotype) is associated with a higher risk of AD and a younger age at dementia onset. We previously found that cognitively normal late-middle-aged APOE epsilon4 carriers have abnormally low CMRgl in the same brain regions as patients with probable Alzheimer's dementia.
Key findings
- Apolipoprotein E (APOE) epsilon4 gene dose (i.e., the number of epsilon4 alleles in a person's APOE genotype) is associated with a higher risk of AD and a younger age at dementia onset.
- We previously found that cognitively normal late-middle-aged APOE epsilon4 carriers have abnormally low CMRgl in the same brain regions as patients with probable Alzheimer's dementia.
- In a PET study of 160 cognitively normal subjects 47-68 years of age, including 36 epsilon4 homozygotes, 46 heterozygotes, and 78 epsilon4 noncarriers who were individually matched for their gender, age, and educational level, we now find that epsilon4 gene dose is correlated with lower CMRgl in each of these brain regions.
- This study raises the possibility of using PET as a quantitative presymptomatic endophenotype to help evaluate the individual and aggregate effects of putative genetic and nongenetic modifiers of AD risk.
Why it matters
In 160 cognitively normal people aged 47 to 68, this PET study examined how APOE ε4 gene dose relates to regional glucose metabolism in the brain. It describes an imaging association in people without dementia and does not test a treatment, cure, or prevention.
Study details
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed 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 | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (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 | 2005 — older than 20 years, still counted |
| 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 | 6 / 7 | Cited 400 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 17.4 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 4 / 6 | Cited 13.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 28 other studies in this library |
| Still being cited | 2 / 4 | Cited 28 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author John Hardy: h-index 205 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | National Institutes of Health: institution h-index 2,723 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15932949) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Reiman, E. M., Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D., et al. (2005). Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.0500579102
Vancouver
Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, et al. Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism. Proceedings of the National Academy of Sciences of the United States of America. 2005. doi:10.1073/pnas.0500579102. PMID: 15932949.
BibTeX
@article{reiman2005-15932949,
author = {Reiman, E. M. and Chen, K. and Alexander, G. E. and Caselli, R. J. and Bandy, D. and Osborne, D. and Saunders, A. M. and Hardy, J.},
title = {{Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2005},
doi = {10.1073/pnas.0500579102},
pmid = {15932949},
url = {https://doi.org/10.1073/pnas.0500579102}
}
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