Browsing by Author "Lee, Dong Young"

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    APOE Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of APOE ε4 on Alzheimer's Disease Risk in a Multiracial Sample
    (MDPI, 2019-08-16) Choi, Kyu Yeong; Lee, Jang Jae; Gunasekaran, Tamil Iniyan; Kang, Sarang; Lee, Wooje; Jeong, Jangho; Lim, Ho Jae; Zhang, Xiaoling; Zhu, Congcong; Won, So-Yoon; Choi, Yu Yong; Seo, Eun Hyun; Lee, Seok Cheol; Gim, Jungsoo; Chung, Ji Yeon; Chong, Ari; Byun, Min Soo; Seo, Sujin; Ko, Pan-Woo; Han, Ji-Won; McLean, Catriona; Farrell, John; Lunetta, Kathryn L.; Miyashita, Akinori; Hara, Norikazu; Won, Sungho; Choi, Seong-Min; Ha, Jung-Min; Jeong, Jee Hyang; Kuwano, Ryozo; Song, Min Kyung; An, Seong Soo A.; Lee, Young Min; Park, Kyung Won; Lee, Ho-Won; Choi, Seong Hye; Rhee, Sangmyung; Song, Woo Keun; Lee, Jung Sup; Mayeux, Richard; Haines, Jonathan L.; Pericak-Vance, Margaret A.; Choo, IL Han; Nho, Kwangsik; Kim, Ki-Woong; Lee, Dong Young; Kim, SangYun; Kim, Byeong C.; Kim, Hoowon; Jun, Gyungah R.; Schellenberg, Gerard D.; Ikeuchi, Takeshi; Farrer, Lindsay A.; Lee, Kun Ho; Radiology and Imaging Sciences, School of Medicine
    Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer's disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10-94; GT: OR = 15.87, p = 2.62 × 10-9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10-108; GT: OR = 12.63, p = 3.44 × 10-64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes.
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    White matter integrity is associated with cognition and amyloid burden in older adult Koreans along the Alzheimer's disease continuum
    (medRxiv, 2023-04-06) Hirschfeld, Lauren Rose; Deardorff, Rachael; Chumin, Evgeny J.; Wu, Yu-Chien; McDonald, Brenna C.; Cao, Sha; Risacher, Shannon L.; Yi, Dahyun; Byun, Min Soo; Lee, Jun-Young; Kim, Yu Kyeong; Kang, Koung Mi; Sohn, Chul-Ho; Nho, Kwangsik; Saykin, Andrew J.; Lee, Dong Young; KBASE Research Group; Radiology and Imaging Sciences, School of Medicine
    Background: White matter (WM) microstructural changes in the hippocampal cingulum bundle (CBH) in Alzheimer's disease (AD) have been described in cohorts of largely European ancestry but are lacking in other populations. Methods: We assessed the relationship between CBH WM integrity and cognition or amyloid burden in 505 Korean older adults aged ≥55 years, including 276 cognitively normal older adults (CN), 142 mild cognitive impairment (MCI), and 87 AD, recruited as part of the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) at Seoul National University. Results: Compared to CN, AD and MCI subjects showed decreased WM integrity in the bilateral CBH. Cognition, mood, and higher amyloid burden were also associated with poorer WM integrity in the CBH. Conclusion: These findings are consistent with patterns of WM microstructural damage previously reported in non-Hispanic White (NHW) MCI/AD cohorts, reinforcing existing evidence from predominantly NHW cohort studies.
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    White matter integrity is associated with cognition and amyloid burden in older adult Koreans along the Alzheimer's disease continuum
    (Springer Nature, 2023-12-16) Hirschfeld, Lauren R.; Deardorff, Rachael; Chumin, Evgeny J.; Wu, Yu‑Chien; McDonald, Brenna C.; Cao, Sha; Risacher, Shannon L.; Yi, Dahyun; Byun, Min Soo; Lee, Jun‑Young; Kim, Yu Kyeong; Kang, Koung Mi; Sohn, Chul‑Ho; Nho, Kwangsik; Saykin, Andrew J.; Lee, Dong Young; KBASE Research Group; Radiology and Imaging Sciences, School of Medicine
    Background: White matter (WM) microstructural changes in the hippocampal cingulum bundle (CBH) in Alzheimer's disease (AD) have been described in cohorts of largely European ancestry but are lacking in other populations. Methods: We assessed the relationship between CBH WM integrity and cognition or amyloid burden in 505 Korean older adults aged ≥ 55 years, including 276 cognitively normal older adults (CN), 142 with mild cognitive impairment (MCI), and 87 AD patients, recruited as part of the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) at Seoul National University. Results: Compared to CN, AD and MCI subjects showed significantly higher RD, MD, and AxD values (all p-values < 0.001) and significantly lower FA values (left p ≤ 0.002, right p ≤ 0.015) after Bonferroni adjustment for multiple comparisons. Most tests of cognition and mood (p < 0.001) as well as higher medial temporal amyloid burden (p < 0.001) were associated with poorer WM integrity in the CBH after Bonferroni adjustment. Conclusion: These findings are consistent with patterns of WM microstructural damage previously reported in non-Hispanic White (NHW) MCI/AD cohorts, reinforcing existing evidence from predominantly NHW cohort studies.