TY - JOUR
T1 - APOEɛ4 genotype, amyloid, and clinical disease progression in cognitively normal older adults
AU - Hollands, Simone
AU - Lim, Yen Ying
AU - Laws, Simon M
AU - Villemagne, Victor L.
AU - Pietrzak, Robert H.
AU - Harrington, Karra
AU - Porter, Tenielle
AU - Snyder, Peter J.
AU - Ames, David
AU - Fowler, Christopher J.
AU - Rainey-Smith, Stephanie R.
AU - Martins, Ralph N
AU - Salvado, Olivier
AU - Robertson, Joanne
AU - Rowe, Christopher C.
AU - Masters, Colin L.
AU - Maruff, Paul
AU - The AIBL Research Group
PY - 2017/3/21
Y1 - 2017/3/21
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Alzheimer type dementia
KW - amyloid-β
KW - apolipoprotein E4
KW - positron emission tomography
UR - http://www.scopus.com/inward/record.url?scp=85041423237&partnerID=8YFLogxK
U2 - 10.3233/JAD-161019
DO - 10.3233/JAD-161019
M3 - Article
C2 - 28234254
SN - 1387-2877
VL - 57
SP - 411
EP - 422
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 2
ER -