The association between Aβ aggregation and age depends on APOE genotype: Findings from the AMYPAD cohort.

Background: The present study aimed to explore the association between Apolipoprotein E (APOE) genotype, the main genetic risk factor for sporadic Alzheimer's Disease (AD), age, and cerebral β‐amyloid (Aβ) aggregation, the earliest pathological event in AD in a large, multicenter, European cohort, the AMYPAD study. Method: We included 876 participants from the AMYPAD cohort who had known APOE genotype and went through at least one Aβ PET imaging. We first looked at the association between Aβ deposition and age according to sex, APOE genotype, and cognitive status. We then used linear regression models to look at the association between Aβ aggregation and APOE genotype in different cerebral regions with age, sex, history of dementia, MMSE score, CDR score, depression, hypercholesterolemia, diabetes and center as covariates. Result: Our participants had a mean age of 67 years old with a mean MMSE score of 28.9/30 and counted 60% of women. We found a positive association between Aβ deposition and age with a gradually stronger association in heterozygous ԑ4 carriers (β (SD) = 1.94 (0.27)) and homozygous ԑ4 carriers (3.18 (0.52)) compared to non‐carriers (0.99 (0.12), p<0.001; Figure). We found similar results when restricting the analyses to cognitively unimpaired participants (heterozygous ԑ4: 1.65 (0.27), p<0.001; homozygous ԑ4: 3.01 (0.52), p<0.001), however Aβ aggregation was less associated to age in participants with mild cognitive impairment (heterozygous ԑ4: 1.33 (1.4), p = 0.33; homozygous ԑ4: 2.34 (1.9), p = 0.29). Moreover, we found an effect of sex on the association between Aβ aggregation and age in ԑ4 non‐carriers characterized by a stronger association in men (1.61 (0.22)) compared to women (0.63 (0.13)). Finally, we observed that the effect of APOE genotype on Aβ aggregation remained similar in the different cerebral regions, with less discernable differences between genotypes in the medial temporal and occipital regions. Conclusion: The number of APOE4 alleles has an impact on the association between age and Aβ aggregation, such that high amyloid was observed at younger ages in homozygous APOE4 carriers than in heterozygous APOE4 carriers and in non‐carriers. The effect of APOE4 on Aβ deposition was global rather than regional in our analysis. [ABSTRACT FROM AUTHOR]