Subjective memory complaints in APOE e4 carriers are associated with high Amyloid-ß Burden

Document Type

Journal Article


IOS Press


School of Medical and Health Sciences




Originally published as: Zwan, M. D., Villemagne, V. L., Doré, V., Buckley, R., Bourgeat, P., Veljanoski, R., ... & Macaulay, S. L. (2016). Subjective memory complaints in APOEɛ4 carriers are associated with high amyloid-β burden. Journal of Alzheimer's Disease, 49(4), 1115-1122. Original article available here


Background: APOE ɛ4 genotype and aging have been identified as risk factors for Alzheimer’s disease (AD). In addition, subjective memory complaints (SMC) might be a first clinical expression of the effect of AD pathology on cognitive functioning. Objective: To assess whether APOE ɛ4 genotype, age, SMC, and episodic memory are risk factors for high amyloid-β (Aβ) burden in cognitively normal elderly. Methods: 307 cognitively normal participants (72.7 ± 6.8 years, 53% female, 55% SMC) from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study underwent amyloid PET and APOE genotyping. Logistic regression analyses were performed to determine the association of APOE ɛ4 genotype, age, SMC, and episodic memory with Aβ pathology. Results: Odds of high Aβ burden were greater at an older age (OR = 3.21; 95% CI = 1.68–6.14), when SMC were present (OR = 1.90; 95% CI = 1.03–3.48), and for APOE ɛ4 carriers (OR = 7.49; 95% CI = 3.96–14.15), while episodic memory was not associated with odds of high Aβ burden. Stratified analyses showed that odds of SMC for high Aβ burden were increased in specifically APOE ɛ4 carriers (OR = 4.58, 95% CI = 1.83–11.49) and younger participants (OR = 3.73, 95% CI = 1.39–10.01). Conclusion: Aging, APOE ɛ4 genotype, and SMC were associated with high Aβ burden. SMC were especially indicative of high Aβ burden in younger participants and in APOE ɛ4 carriers. These findings suggest that selection based on the presence of SMC, APOE ɛ4 genotype and age may help identify healthy elderly participants with high Aβ burden eligible for secondary prevention trials.