title: APOEɛ4 Genotype, Amyloid, and Clinical Disease Progression in Cognitively Normal Older Adults.
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.
authors.affiliation: La Trobe University, Melbourne, VIC, Australia.
authors.forename: Simone
authors.initials: S
authors.lastname: Hollands
authors.affiliation: The Florey Institute, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Yen Ying
authors.initials: YY
authors.lastname: Lim
authors.affiliation: 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, http://www.mentalhealthcrc.com.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Laws
authors.affiliation: The Florey Institute, The University of Melbourne, Parkville, VIC, Australia.|Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia.|Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC, Australia.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Pietrzak
authors.affiliation: The Florey Institute, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Karra
authors.initials: K
authors.lastname: Harrington
authors.affiliation: 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, http://www.mentalhealthcrc.com.
authors.forename: Tenielle
authors.initials: T
authors.lastname: Porter
authors.affiliation: Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Snyder
authors.affiliation: Academic Unit for Psychiatry of Old Age, St. Vincent's Health, The University of Melbourne, Kew, VIC, Australia.|National Ageing Research Institute, Parkville, VIC, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: The Florey Institute, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Fowler
authors.affiliation: 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.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Rainey-Smith
authors.affiliation: 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.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.affiliation: Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship, Australian e-Health Research Centre-BiaMedIA, Brisbane, QLD, Australia.
authors.forename: Olivier
authors.initials: O
authors.lastname: Salvado
authors.affiliation: The Florey Institute, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Robertson
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia.|Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC, Australia.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
authors.affiliation: The Florey Institute, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: The Florey Institute, The University of Melbourne, Parkville, VIC, Australia.|Cogstate Ltd., Melbourne, VIC, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Maruff
mesh_terms: D000368:Aged; D000682:Amyloid / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001315:Australia; D001921:Brain / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D060005:Genotyping Techniques; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000682:Amyloid; D053327:Apolipoprotein E4
keywords: Alzheimer type dementia; Alzheimer’s disease; amyloid-β; apolipoprotein E4; positron emission tomography