Objective:

To compare cortical thickness across APOE genotypes, and to assess the potential protective effect of APOE2 on brain cortical thinning and grey matter volume.

Background:

Studies have shown a negative association of APOE-ε4 allele with regional cortical thickness and volume. The role of the APOE-ε3 allele has been considered neutral in several studies. The protective role of APOE-ε2 against cortical thinning has not been well established.

Design/Methods:

From a biomarker cerebrovascular registry, 187 individuals with APOE testing and MRI brain from 2010 to 2020 were included. APOE genotype tested were ε2ε2, ε2ε3, ε2ε4, ε3ε3, ε3ε4, ε4ε4, stratified to APOE-ε2 carrier or APOE-ε2 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 ε2 vs non-ε2 allele carriers. Mini-Mental Status Examination (MMSE) were compared between groups.

Results:

In our cohort (n=187), mean age was 60±16 years and 55.4% were female. Of the APOE genotypes, 18.5% were APOE-ε2 carriers (ε2ε2 3, ε2ε3 33), 81.5% were APOE-ε2 non-carriers (ε3ε3 114, ε3ε4 43, ε4ε4 2). Compared to ε2 non-carriers, ε2 carriers were less likely to have hypertension, diabetes, coronary artery disease, and had higher LDL (p<0.05). Across APOE genotypes, cortex was thickest in ε2ε2 (2.35 mm) and thinnest in ε4ε4 (1.92 mm) (p = 0.0137). APOE-ε2 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=<0.001) and grey matter volumes (459.93 cm3 vs 411.01 cm3, p=0.001), compared to ε2 non-carriers. There was no difference in MMSE between ε2carriers vs non-carriers (24.4 vs 25.6, p=0.316).

Conclusions:

Our study suggested a protective effect of APOE-ε2 allele against cortical thinning and grey matter volume loss. Future study may examine the effect of APOE-ε2 on brain resilience after brain injury such as stroke.