Ic‐p‐071: The Effect of Apoe on White Matter Lesions

The influence of the Apolipoprotein E (APOE) gene on white matter lesions (WMLs) is still controversial: some studies found increased WMLs in ε2 carriers, others in ε4, whereas others reported no significant effect (Cherbuin et al., 2007). The present work investigates the effect of APOE on white matter damage and explores whether a possible interaction of APOE with age and gender may clarify these inconsistent pattern of findings. We selected from the ARWIBO database (http://www.arwibo.it) the 405 cognitively healthy persons (age: Mean±SD: 57.5±10.5) having both axial-FLAIR MRI scan and APOE characterization. Two experts consensually rated WMLs using the Age-Related White Matter Changes (ARWMC; Wahlund et al.,2001) scale. Participants were stratified into middle-aged (range 40-59; N=229) and elders (range 60-84; N=176). A generalized linear model fitting a Poisson distribution was performed using ARWMC Global Score (GS) as dependent variable, APOE genotype (ε2/ε3; ε3/ε4; ε3/ε3), gender and their interaction as independent variables. GS was significantly greater in ε2/ε3 than ε3/ε3 and ε3/ε4 (all p<0.05, Table).The interaction between gender and APOE status was significant in the elders (p<0.001). Pairwise comparisons showed that elderly females carrying the ε2/ε3 genotype reported far higher GS than any other elderly group (all p<0.001, Table). APOE-ε2/ε3 might be a risk factor for WMLs. This finding is in line with those obtained in cerebral amyloid angiopathy (Lemmens et al., 2007) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (Gesierich et al, 2016) reporting a higher amount of WMLs in APOE-ε2, but not in APOE-ε4, compared with APOE-ε3 carriers. Moreover, when considering the interaction of APOE alleles with age and gender, the APOE-ε2 allele emerges as consistently associated to increased WMLs in females ε2/ε3-carriers over-60. References: Cherbuin et al. Dement. Geriatr. Cogn. Disord. 2007;24(5):348-6 ARWIBO. Retrieved from http://www.arwibo.it/. Wahlund et al. Stroke. 2001;32(6):1818-22 Lemmens et al. Stroke. 2007;38(4):1185-8 Gesierich et al. Cereb. Blood. Flow. Metab. 2016;36(1):199-203.