Protective Effect of APOE-ɛ2 on Cortical Thickness and Volume in a Cerebrovascular Registry (S36.010)

Abstract

<h3>Objective:</h3> To compare cortical thickness across APOE genotypes, and to assess the potential protective effect of APOE2 on brain cortical thinning and grey matter volume. <h3>Background:</h3> Studies have shown a negative association of APOE-ɛ4 allele with regional cortical thickness and volume. The role of the APOE-ɛ3 allele has been considered neutral in several studies. The protective role of APOE-ɛ2 against cortical thinning has not been well established. <h3>Design/Methods:</h3> From a biomarker cerebrovascular registry, 187 individuals with APOE testing and MRI brain from 2010 to 2020 were included. APOE genotype tested were ɛ2ɛ2, ɛ2ɛ3, ɛ2ɛ4, ɛ3ɛ3, ɛ3ɛ4, ɛ4ɛ4, stratified to APOE-ɛ2 carrier or APOE-ɛ2 non-carrier. Cortical thickness, cortical volume and gray matter volume were estimated on T1-weighted images using FreeSurfer. Measures of brain atrophy were compared across APOE genotypes, and between ɛ2 vs non-ɛ2 allele carriers. Mini-Mental Status Examination (MMSE) were compared between groups. <h3>Results:</h3> In our cohort (n=187), mean age was 60±16 years and 55.4% were female. Of the APOE genotypes, 18.5% were APOE-ɛ2 carriers (ɛ2ɛ2 3, ɛ2ɛ3 33), 81.5% were APOE-ɛ2 non-carriers (ɛ3ɛ3 114, ɛ3ɛ4 43, ɛ4ɛ4 2). Compared to ɛ2 non-carriers, ɛ2 carriers were less likely to have hypertension, diabetes, coronary artery disease, and had higher LDL (p&lt;0.05). Across APOE genotypes, cortex was thickest in ɛ2ɛ2 (2.35 mm) and thinnest in ɛ4ɛ4 (1.92 mm) (p = 0.0137). APOE-ɛ2 carriers had significantly thicker cortex (2.13 mm vs 1.96 mm, p=0.001), larger cortical volume (313.26 cm3 vs 266.09 cm3, p=&lt;0.001) and grey matter volumes (459.93 cm3 vs 411.01 cm3, p=0.001), compared to ɛ2 non-carriers. There was no difference in MMSE between ɛ2carriers vs non-carriers (24.4 vs 25.6, p=0.316). <h3>Conclusions:</h3> Our study suggested a protective effect of APOE-ɛ2 allele against cortical thinning and grey matter volume loss. Future study may examine the effect of APOE-ɛ2 on brain resilience after brain injury such as stroke. <b>Disclosure:</b> Mr. Youssef has nothing to disclose. Mr. Mateti has nothing to disclose. Erik Middlebrooks has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Varian Medical Systems Inc. Erik Middlebrooks has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific Corp. The institution of Erik Middlebrooks has received research support from Varian Medical Systems Inc. The institution of Dr. Taner has received research support from NIH. The institution of Dr. Meschia has received research support from NINDS. The institution of Dr. Meschia has received research support from NINDS. Dr. Lin has nothing to disclose.