Apolipoprotein E4 Affects Topographical Changes in Hippocampal and Cortical Atrophy in Alzheimer's Disease Dementia: A Five-Year Longitudinal Study

Article type: Research Article

Authors: Kim, Yeo Jin^{a; b} | Cho, Hanna^c | Kim, Yun Joong^d | Ki, Chang-Seok^e | Chung, Sun Ju^f | Ye, Byoung Seok^g | Kim, Hee Jin^{a; b} | Kim, Jung-Hyun^a | Kim, Sung Tae^h | Lee, Kyung Hanⁱ | Jeon, Seun^j | Lee, Jong-Min^j | Chin, Juhee^{a; b} | Kim, Jeong-Hun^k | Na, Duk L.^{a; b} | Seong, Joon-Kyung^l | Seo, Sang Won^{a; b; *}

Affiliations: [a] Department of Neurology, Sungkyunkwan University School of Medicine, Seoul, Korea | [b] Neuto Science Center, Samsung Medical Center, Seoul, Republic of Korea | [c] Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea | [d] Department of Neurology, Ilsong Institute of Life Science, Hallym University, Anyang, Korea | [e] Department of Laboratory Medicine & Genetics, Sungkyunkwan University School of Medicine, Seoul, Korea | [f] Department of Neurology, Asan Medical Center, Ulsan University School of Medicine, Seoul, Korea | [g] Department of Neurology, Yonsei University College of Medicine, Seoul, Korea | [h] Department of Radiology, Sungkyunkwan University School of Medicine, Seoul, Korea | [i] Department of Nuclear Medicine and, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea | [j] Department of Biomedical Engineering, Hanyang University, Seoul, Korea | [k] Department of Computer and Radio Communications Engineering, Korea University, Seoul, Republic of Korea | [l] Department of Biomedical Engineering, Korea University, Seoul, Republic of Korea

Correspondence: [*] Correspondence to: Sang Won Seo, MD, PhD, Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center, 50 Ilwon-dong, Gangnam-gu, Seoul 135–710, Republic of Korea. Tel.: +82 2 3410 1233; Fax: +82 2 3410 0052; E-mail: [email protected].

Abstract: Apolipoprotein E4 (APOE4) is a genetic risk factor for developing Alzheimer's disease (AD). Once AD manifests clinically, however, the effects of APOE4 are less clear. Therefore, we investigated the longitudinal effects of APOE4 on topographical changes in AD patient brain atrophy. We prospectively recruited 35 patients with AD (19 APOE4 carriers and 16 non-carriers), and 14 normal controls, then followed them for five years. We measured hippocampal deformities and cortical thickness. Hippocampal comparison between APOE4 carriers and non-carriers with AD showed carriers had rapid changes in the head and body, while non-carriers had rapid changes in a small portion of the body. Cortical thickness comparison between APOE4 carriers and non-carriers with AD dementia showed carriers had rapid thinning in the lateral frontal, temporal, and parietal regions, while no region showed more rapid cortical thinning in non-carriers than in carriers. These findings underlined the importance of the APOE4 allele for designing and interpreting future treatment trials in patients with AD dementia.

Keywords: APOE4 allele, cortical thickness, dementia with Alzheimer's disease, hippocampal deformities, longitudinal study

DOI: 10.3233/JAD-141773

Journal: Journal of Alzheimer's Disease, vol. 44, no. 4, pp. 1075-1085, 2015