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Title: APOEɛ4 Genotype, Amyloid, and Clinical Disease Progression in Cognitively Normal Older Adults.
Austin Authors: Hollands, Simone;Lim, Yen Ying;Laws, Simon M;Villemagne, Victor L ;Pietrzak, Robert H;Harrington, Karra;Porter, Tenielle;Snyder, Peter;Ames, David;Fowler, Christopher;Rainey-Smith, Stephanie R;Martins, Ralph N;Salvado, Olivier;Robertson, Joanne;Rowe, Christopher C ;Masters, Colin L ;Maruff, Paul
Affiliation: Cogstate Ltd., Melbourne, Victoria, Australia
La Trobe University, Melbourne, Victoria, Australia
Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, WA, Australia
Co-operative Research Centre for Mental Health,
The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia
Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI, USA
Academic Unit for Psychiatry of Old Age, St. Vincent's Health, The University of Melbourne, Kew, Victoria, Australia
National Ageing Research Institute, Parkville, Victoria, Australia
Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship, Australian e-Health Research Centre-BiaMedIA, Brisbane, QLD, Australia
Issue Date: 2017
Publication information: Journal of Alzheimer's disease : JAD 2017; 57(2): 411-422
Abstract: 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. To determine the extent and nature to which APOEɛ4 increases risk for clinical disease progression in CN older adults. 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. 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. 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
ORCID: 0000-0003-3910-2453
Journal: Journal of Alzheimer's disease : JAD
PubMed URL: 28234254
Type: Journal Article
Subjects: Alzheimer type dementia
Alzheimer’s disease
apolipoprotein E4
positron emission tomography
Appears in Collections:Journal articles

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