Journal article
APOE ɛ4 genotype, amyloid, and clinical disease progression in cognitively normal older adults
Journal of Alzheimer's disease : JAD, Vol.57(2), pp.411-422
2017
Abstract
Background: In cognitively normal (CN) older adults, carriage of the apolipoprotein E (APOE) ɛ4 allele is associated with increased risk for dementia of the Alzheimer type (AD-dementia). It is unclear whether this occurs solely through APOEɛ4 increasing amyloid-β (Aβ) accumulation or through processes independent of Aβ.
Objective: To determine the extent and nature to which APOEɛ4 increases risk for clinical disease progression in CN older adults.
Methods: Data from the total (n = 765) and Aβ-imaged (n = 423) CN cohort in the Australian Imaging, Biomarker and Lifestyle (AIBL) Study of Ageing was analyzed using Cox proportional hazard models to estimate ɛ4 risk for clinical disease progression over a 72-month follow-up.
Results: With Aβ status unknown and risk from demographic characteristics controlled, ɛ4 carriage increased risk for clinical disease progression over 72 months by 2.66 times compared to risk of non-ɛ4 carriage. Re-analysis with Aβ status included showed that abnormally high Aβ increased risk for clinical disease progression over 72 months by 2.11 times compared to risk of low Aβ. However, with Aβ level known, ɛ4 carriage was no longer predictive of clinical disease progression.
Conclusion: In CN older adults, the risk of ɛ4 for clinical disease progression occurs through the effect of ɛ4 increasing Aβ levels.
Details
- Title
- APOE ɛ4 genotype, amyloid, and clinical disease progression in cognitively normal older adults
- Authors/Creators
- S. Hollands (Author/Creator) - La Trobe UniversityY.Y. Lim (Author/Creator) - Florey Institute of Neuroscience and Mental HealthS.M. Laws (Author/Creator) - Edith Cowan UniversityV.L. Villemagne (Author/Creator) - Florey Institute of Neuroscience and Mental HealthR.H. Pietrzak (Author/Creator) - Yale UniversityK. Harrington (Author/Creator) - Florey Institute of Neuroscience and Mental HealthT. Porter (Author/Creator)P. Snyder (Author/Creator) - Brown UniversityD. Ames (Author/Creator) - St Vincent's HealthC. Fowler (Author/Creator) - Florey Institute of Neuroscience and Mental HealthS.R. Rainey-Smith (Author/Creator) - Edith Cowan UniversityR.N. Martins (Author/Creator) - Edith Cowan UniversityO. Salvado (Author/Creator) - Australian e-Health Research CentreJ. Robertson (Author/Creator) - Florey Institute of Neuroscience and Mental HealthC.C. Rowe (Author/Creator) - Austin HealthC.L. Masters (Author/Creator) - Florey Institute of Neuroscience and Mental HealthP. Maruff (Author/Creator) - Florey Institute of Neuroscience and Mental Health
- Publication Details
- Journal of Alzheimer's disease : JAD, Vol.57(2), pp.411-422
- Publisher
- IOS Press
- Identifiers
- 991005540913007891
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- 1.52 Neurodegenerative Diseases
- 1.52.60 Dementia
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