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Apolipoprotein E ε4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease
Fleisher AS, Chen K, Liu X, Ayutyanont N, Roontiva A, Thiyyagura P, Protas H, Joshi AD et al.. Neurobiology of aging, 2012-05-24
Topic: Brain proteins, microglia and lab models
Objectives Investigate apolipoprotein E ε4 (APOE4) gene and aging effects on florbetapir F18 positron emission tomography (PET) in normal aging and Alzheimer's disease (AD). Methods Florbetapir F18 PET images were analyzed from 245 participants, 18-92 years of age, from Avid Radiopharmaceutical's multicenter registered trials, including 86 younger healthy control volunteers (yHC), 61 older healthy control volunteers (oHC), 53 mild cognitive impairment (MCI) patients, and 45 AD dementia patients (DAT). Mean florbetapir standard uptake value ratios (SUVRs) were used to evaluate the effects of APOE4 carrier status, older age, and their interaction in each of these groups. Results In comparison with non-carriers, the APOE4 carriers in each of the oHC, MCI, and DAT groups had higher mean cortical-to-cerebellar florbetapir SUVRs, patterns of florbetapir PET elevations characteristic of DAT, and a higher proportion meeting florbetapir PET positivity criteria. Only the oHC group had a significant association between mean cortical florbetapir SUVRs and age. In cognitively normal adults, without regards to APOE4 genotype, amyloid began to increase at age 58 (95% confidence interval [CI]: 52.3-63.7), with a predicted typical age of florbetapir positivity occurring around age 71 years. Presence of the APOE4 gene reduced the age of predicted florbetapir positivity in normal aging to around age 56 years, approximately 20 years younger than non-carriers. Interpretation Cerebral amyloid deposition is associated with APOE4 carrier status in older healthy control subjects and symptomatic AD patients, and increases with age in older cognitively normal individuals. Amyloid imaging positivity appears to begin near age 56 years in cognitively intact APOE4 carriers and age 76 years in APOE4 non-carriers.
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APA 7th
Fleisher, A. S., Chen, K., Liu, X., Ayutyanont, N., Roontiva, A., Thiyyagura, P., et al. (2013). Apolipoprotein E ε4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2012.04.017
Vancouver
Fleisher AS, Chen K, Liu X, Ayutyanont N, Roontiva A, Thiyyagura P, et al. Apolipoprotein E ε4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease. Neurobiology of aging. 2013. doi:10.1016/j.neurobiolaging.2012.04.017. PMID: 22633529.
BibTeX
@article{fleisher2013-22633529,
author = {Fleisher, A. S. and Chen, K. and Liu, X. and Ayutyanont, N. and Roontiva, A. and Thiyyagura, P. and Protas, H. and Joshi, A. D. and others},
title = {{Apolipoprotein E ε4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease}},
journal = {Neurobiology of aging},
year = {2013},
doi = {10.1016/j.neurobiolaging.2012.04.017},
pmid = {22633529},
url = {https://doi.org/10.1016/j.neurobiolaging.2012.04.017}
}
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Key findings
- Results In comparison with non-carriers, the APOE4 carriers in each of the oHC, MCI, and DAT groups had higher mean cortical-to-cerebellar florbetapir SUVRs, patterns of florbetapir PET elevations characteristic of DAT, and a higher proportion meeting florbetapir PET positivity criteria.
- Only the oHC group had a significant association between mean cortical florbetapir SUVRs and age.
- Interpretation Cerebral amyloid deposition is associated with APOE4 carrier status in older healthy control subjects and symptomatic AD patients, and increases with age in older cognitively normal individuals.
Why it matters
In florbetapir PET scans of 245 people aged 18–92, APOE4 carriers who were older and healthy, had mild cognitive impairment, or had Alzheimer dementia showed more amyloid than non-carriers, and amyloid rose with age only in the older healthy group. In cognitively normal adults amyloid began to increase around age 58, and the authors predicted that scans would typically turn amyloid-positive near age 56 in APOE4 carriers versus 76 in non-carriers. These are group-level estimates of when amyloid appears on a scan, not of when symptoms start, and the study tested no treatment.
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Study details
- Participants245
- Evidence strengthLow
How this study scored 56/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of aging) |
| Journal's citation record | 3 / 4 | Neurobiology of Aging: journal h-index 263 (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 | 2 / 4 | 245 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 208 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.9 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 4 / 6 | Cited 12.7× 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 33 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Eric M. Reiman: h-index 151 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 15 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22633529) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
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