J Korean Neurol Assoc > Volume 20(6); 2002 > Article

Journal of the Korean Neurological Association 2002;20(6): 641-651.

"산발형 알쯔하이머병 환자의 뇌 조직에서 Apolipoprotein E 유전자와 Alpha 1-antichymotrypsin 유전자 검사"

김상호, 한서영 최영숙 이광수

가톨릭대학교 의과대학 병리학교실,신경과학교실

"Apolipoprotein E Gene and Alpha 1-Antichymotrypsin Gene in Brain of Sporadic Alzheimer s Disease"

Sang-Ho Kim, M.D.

"Department of Pathology, College of Medicine, The Catholic University of Korea Department of Neurology, College of Medicine, The Catholic University of Korea"

Abstract

"Background : This study aims to detect any causative genetic alterations and to demonstrate any correlations of these genes in the pathogenesis of mostly late-occurring sporadic type of Alzheimer s disease (AD). Methods : A total of 67 registered cases of autopsy-confirmed brain tissues were analyzed. Included here was sporadic AD (n=41), vascular dementia (n=17), and non-demented physiologically aging control brains (n=9). ApoE genotyping was done with the enzymatic digestion, and allele specific PCR was done to analyze the -491 A/T polymorphism of ApoE. Detection of polymorphism of alpha 2-macroglobulin (A2M) was done with enzymatic digestion and DNA sequencing. RT-PCR products were electrophoresed to detect mRNA expression of alpha 1-antichymotrypsin (ACT). Results : A prevalence rate of ApoE E4 genotype (E3/E4, E4/E4) showed significantly higher in patients with AD than in patients with vascular dementia (43.8% vs. 11.7%, p=0.019). Only 1 out of 4 cases of sporadic AD was associated with the E4/E4 allele. -491A/ T polymorphism of the ApoE promoter was found only in AD (2/41 cases, 4.9%). The incidence of heterozygous allelic polymorphism with 5 bp deletions in exon 18 of A2M-2 was 4.9% (2 out of 41) in AD. Messenger RNA expres-sion of ACT, which is closely associated with the ApoE E4 allele, was increased in AD in comparison with normal con-trol (p=0.0002). Conclusions : ApoE4 genotype and ACT are closely related to the pathogenesis of late-onset sporadic AD. Neither -491 polymorphism of ApoE promoter nor A2M-2 showed close association with AD in these brain sam-ples.Key Words : Alzheimer s disease, Polymorphism, Apolipoprotein E, Alpha 1-antichymotrypsin, Alpha 2-macroglobulin"