A genetic screen of the mutations in the Korean patients with early-onset Alzheimer’s disease

Seong Soo An, Sun Ah Park, Eva Bagyinszky, Sun Oh Bae, Yoon Jeong Kim, Ji Young Im, Kyung Won Park, Kee Hyung Park, Eun Joo Kim, Jee Hyang Jeong, Jong Hun Kim, Hyun Jeong Han, Seong Hye Choi, Sangyun Kim

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20 Scopus citations


Early-onset Alzheimer’s disease (EOAD) has distinct clinical characteristics in comparison to late-onset Alzheimer’s disease (LOAD). The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS) study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer’s disease (AD) mutations in the consecutive EOAD subjects from the CREDOS study from April 2012 to February 2014. We checked the sequence of APP (exons 16−17), PSEN1 (exons 3−12), and PSEN2 (exons 3−12) genes. We identified different causative or probable pathogenic AD mutations, PSEN1 T116I, PSEN1 L226F, and PSEN2 V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia. PSEN1 T116I case demonstrated autosomal dominant trait of inheritance, with at least 11 affected individuals over 2 generations. However, there was no family history of dementia within first-degree relation in PSEN1 L226F and PSEN2 V214L cases. Approximately, 55.7% of the EOAD subjects had APOE ε4 allele, while none of the mutation-carrying subjects had the allele. The frequency of genetic mutation in this study is lower compared to the studies from other countries. The study design that was based on nationwide cohort, which minimizes selection bias, is thought to be one of the contributors to the lower frequency of genetic mutation. However, the possibility of the greater likeliness of earlier onset of sporadic AD in Korea cannot be excluded. We suggest early AD onset and not carrying APOE ε4 allele are more reliable factors for predicting an induced genetic mutation than the presence of the family history in Korean EOAD population.

Original languageEnglish
Pages (from-to)1817-1822
Number of pages6
JournalClinical Interventions in Aging
StatePublished - 15 Dec 2016

Bibliographical note

Funding Information:
This work was supported by grants from the Korea Health Technology R&D Project (HI10C2020, HI14C1942, and HI14C3331) through the Korea Health Industry Development Institute (KHIDI), Korea Ministry of Health & Welfare, and the Original Technology Research Program for Brain Science through the National Research Foundation of Korea funded by the Korean Government (MSIP; No 2014M3C7A1064752).Genetic screening has been performed by Department of Bionano Technology, Gachon University. For the current study, blood samples were collected from the patients with informed consent at Soonchunhyang University Bucheon Hospital, Republic of Korea; Dong-A University Medical Center, Busan, Republic of Korea; Gachon University, Gil Medical Center, Incheon, Korea; Pusan National University Hospital, Busan, Republic of Korea; Ewha Womans University Mokdong Hospital, Seoul, Republic of Korea; Ilsan Hospital, National Health Insurance Corporation, Goyang, Republic of Korea; Myongii Hospital, Goyang, Republic of Korea; Inha University School of Medicine, Incheon, Republic of Korea. The Ethical Committee of the Soonchunhyang University Bucheon Hospital, Seoul National University College of Medicine & Neurocognitive Behavior Center, and Seoul National University Bundang Hospital approved the current study.

Publisher Copyright:
© 2016 An et al.


  • Alzheimer’s disease
  • Apolipoprotein-E
  • Early onset Alzheimer’s disease
  • Genetics
  • Mutation
  • Presenilin
  • Sequencing


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