Apolipoprotein E ε4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease
Abstract
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 depo…
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APOE's role in promoting β-amyloid plaque pathology in Alzheimer's disease is well established.
“In AD, its specific role in promoting β-amyloid (Aβ) plaque pathology is, however, well established (Fleisher et al, 2013; Kok et al, 2009; Murphy et al, 2013; Schmechel et al, 1993).”
From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Fleisher et al, 2013
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- Authors
- Fleisher, A. S., Chen, K., Liu, X., Ayutyanont, N., Roontiva, A., Thiyyagura, P., Protas, H., Joshi, A. D., Sabbagh, M., Sadowsky, C. H., Sperling, R. A., Clark, C. M., Mintun, M. A., Pontecorvo, M. J., Coleman, R. E., Doraiswamy, P. M., Johnson, K. A., Carpenter, A. P., Skovronsky, D. M., & Reiman, E. M.
- Affiliations
- University of California San Diego (US)
- Banner Alzheimer’s Institute (US)
- Avid Radiopharmaceuticals (United States) (US)
- Banner Health (US)
- Nova Southeastern University (US)
- Brigham and Women's Hospital (US)
- Washington University in St. Louis (US)
- Duke Medical Center (US)
- Corresponding author
- Fleisher, Adam S.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 34
- Issue
- 1
- Pages
- 1-12
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2047125512
- Cited by
- 202
- References
- 15
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 18 · 2023: 6 · 2022: 15 · 2021: 18 · 2020: 17 · 2019: 12 · 2018: 6 · 2017: 21 · 2016: 15 · 2015: 20 · 2014: 18 · 2013: 22 · 2012: 2
- FWCI
- 13.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- 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, florbetapir, amyloid PET, Alzheimer's disease, normal aging, mild cognitive impairment, age effects, cerebral amyloid deposition, genetic risk factors, healthy older adults
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Analysis of Variance, Aniline Compounds, Brain, Brain Mapping, Ethylene Glycols, Humans, Mental Status Schedule, Middle Aged, Positron-Emission Tomography, Apolipoprotein E4, Young Adult, Cognitive Dysfunction
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