J Korean Neurol Assoc.  2002 Nov;20(6):641-651.

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

• Kim SH
• Han SY
• Choi YS
• Lee KS

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.

Keyword

Alzheimer's disease; Polymorphism; Apolipoprotein E; Alpha 1-antichymotrypsin; Alpha 2-macroglobulin

MeSH Terms

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
Apolipoprotein E4
Apolipoproteins
Apolipoproteins E
RNA, Messenger
alpha 1-Antichymotrypsin
alpha-Macroglobulins