APOE e4 genotype, amyloid, and clinical disease progression in cognitively normal older adults

Authors

Simone Hollands
Yen Ying Lim
Simon Laws, Edith Cowan UniversityFollow
Victor L. Villemagne
Robert Pietrzak
Karra Harrington
Tenielle Porter, Edith Cowan UniversityFollow
Peter Snyder
David Ames
Christopher Fowler
Stephanie Rainey-Smith, Edith Cowan UniversityFollow
Ralph Martins, Edith Cowan UniversityFollow
Oliver Salvado
Joanne Robertson
Christopher C. Rowe
Colin L. Masters
Paul Maruff

Document Type

Journal Article

Publication Title

Journal of Alzheimer's Disease

Publisher

IOS Press

School

Centre of Excellence for Alzheimer’s Disease Research and Care / School of Medical and Health Sciences

RAS ID

23622

Comments

Hollands, S., Lim, Y. Y., Laws, S. M., Villemagne, V. L., Pietrzak, R. H., Harrington, K., . . . Rainey-Smith, S. R. (2017). APOEɛ4 genotype, amyloid, and clinical disease progression in cognitively normal older adults. Journal of Alzheimer's Disease. 57(2) 411-422. https://doi.org/10.3233/JAD-161019

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 APOE ɛ4 increasing amyloid-β (Aβ) accumulation or through processes independent of Aβ.

Objective: To determine the extent and nature to which APOE ɛ4 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.

DOI

10.3233/JAD-161019

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