Apolipoprotein E Gene and Alpha 1-Antichymotrypsin Gene in Brain of Sporadic Alzheimer's Disease.
- Author:
Sang Ho KIM
1
;
Seo Young HAN
;
Young Sook CHOI
;
Kwang Soo LEE
Author Information
1. Department of Pathology, College of Medicine, The Catholic University of Korea, Korea.
- Publication Type:Original Article
- Keywords:
Alzheimer's disease;
Polymorphism;
Apolipoprotein E;
Alpha 1-antichymotrypsin;
Alpha 2-macroglobulin
- MeSH:
Aging;
Alleles;
alpha 1-Antichymotrypsin*;
alpha-Macroglobulins;
Alzheimer Disease*;
Apolipoprotein E4;
Apolipoproteins E;
Apolipoproteins*;
Brain*;
Dementia, Vascular;
Digestion;
Exons;
Genotype;
Humans;
Incidence;
Polymerase Chain Reaction;
Prevalence;
RNA, Messenger;
Sequence Analysis, DNA
- From:Journal of the Korean Neurological Association
2002;20(6):641-651
- CountryRepublic of Korea
- Language:Korean
-
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 expression of ACT, which is closely associated with the ApoE E4 allele, was increased in AD in comparison with normal control (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 samples.
