P1‐383: APOE‐ε4 IS ASSOCIATED WITH LESS ANTERIOR CINGULATE CORTEX AND INFERIOR FRONTAL GYRUS THICKNESS IN LATE‐ONSET AD

Abstract

The ApoE-ε4 is a well-proven genetic risk factor for late-onset Alzheimer's disease (LOAD). However, how the epsilon4 allele contributes to disease pathophysiology and the relationship between clinical phenotype are still unclear. This study is aim to explore the association between ApoE-ε4 and regional cortical thickness and brain volume in LOAD to better understand the effect of ApoE-ε4 on LOAD. Patients diagnosed with probable AD by NIA-AA 2011 criteria were recruited from Dementia Clinic in Pecking Union Medical College Hospital. Patients with initial symptoms developed after age of 65 were included. Data including basic population information, history, physical examination, psychological assessment, MRI and ApoE genotype were collected. Using T1-weight imaging, regional cortical thickness and brain volume of whole cerebral were analyzed by DR.BRAIN software. Multiple linear regression models were applied for analyze factors including ApoE-ε4 and disease severity(reflected by ADL score) of affecting the separate regional cortical thickness. 43 LOAD patients were included in this study. As for the analysis of regional cortical thickness: LOAD patient without ApoE-ε4 showed less cortical thickness compared to patients carrying ApoE-ε4 in left pars orbitalis(F(2,36)=3.811 (P<0.05), adjust R2=0.129), left rostral anterior cingulate(F(2,36)=6.078 (P<0.05), adjust R2=0.211), left caudal anterior cingulate(F(2,36)=5.561 (P<0.05), adjust R2=0.194), right pars triangularis (F(2,36)=3.390 (P<0.05), adjust R2=0.112) and right isthmus cingulate cortex thickness (F(2,36)=3.390 (P<0.05), adjust R2=0.120). As for the analysis of regional brain volume: LOAD patient without ApoE-ε4 showed less atrophy compared to patients carrying ApoE-ε4 in left caudal anterior cingulate (F(2,36)=3.589 (P<0.05), adjust R2=0.120), left paracentral (F(2,36)=6.580 (P<0.05), adjust R2=0.227) regions. We found less cortical thickness in bilateral anterior cingulate and inferior frontal gyrus and less atrophy in left caudal anterior cingulate and paracentral regions are associated with the absence of ApoE-ε4 in LOAD patients. These data suggest a region-specific biological effect of the e4 allele in the brains of LOAD patients. This work was supported by CAMS Innovation fund for medical sciences (2016-I2M-1-004), National Natural Science Foundation of China (81550021), 13th Five year National Key Research and Development Program of China (2016YFC1306300), The strategic priority research program (Pilot study)”biological basis of aging and therapeutic strategies” of the Chinese Academy of Sciences (grant XDPB10).