title: A genetic screen of the mutations in the Korean patients with early-onset Alzheimer's disease.
abstract: 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 ofAPP(exons 16-17),PSEN1(exons 3-12), andPSEN2(exons 3-12) genes. We identified different causative or probable pathogenic AD mutations,PSEN1T116I,PSEN1L226F, andPSEN2V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia.PSEN1T116I 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 inPSEN1L226F andPSEN2V214L cases. Approximately, 55.7% of the EOAD subjects hadAPOEε4 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 carryingAPOEε4 allele are more reliable factors for predicting an induced genetic mutation than the presence of the family history in Korean EOAD population.
authors.affiliation: Department of Bionano Technology, Gachon University, Seongnam-si.
authors.forename: Seong Soo
authors.initials: SS
authors.lastname: An
authors.affiliation: Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon.
authors.forename: Sun Ah
authors.initials: SA
authors.lastname: Park
authors.affiliation: Department of Bionano Technology, Gachon University, Seongnam-si.
authors.forename: Eva
authors.initials: E
authors.lastname: Bagyinszky
authors.affiliation: Department of Bionano Technology, Gachon University, Seongnam-si.
authors.forename: Sun Oh
authors.initials: SO
authors.lastname: Bae
authors.affiliation: Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon.
authors.forename: Yoon-Jeong
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Im
authors.affiliation: Department of Neurology, Dong-A University College of Medicine and Institute of Convergence Bio-Health, Busan.
authors.forename: Kyung Won
authors.initials: KW
authors.lastname: Park
authors.affiliation: Department of Neurology, Gachon University Gil Medical Center, Incheon.
authors.forename: Kee Hyung
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Neurology, Pusan National University Hospital, Busan.
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Ewha Womans University Mokdong Hospital, Seoul.
authors.forename: Jee Hyang
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Neurology, Ilsan Hospital, National Health Insurance Corporation.
authors.forename: Jong Hun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Neurology, Myongii Hospital, Goyang.
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Han
authors.affiliation: Department of Neurology, Inha University School of Medicine, Incheon.
authors.forename: Seong Hye
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
authors.forename: SangYun
authors.initials: S
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D053764:Presenilin-1 / Q000235:genetics; D053766:Presenilin-2 / Q000235:genetics; D056910:Republic of Korea / Q000453:epidemiology
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2
keywords: Alzheimer’s disease; apolipoprotein-E; early onset Alzheimer’s disease; genetics; mutation; presenilin; sequencing