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Molecular genetic and pathologic stu...
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Chen, Lan.
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Molecular genetic and pathologic studies of Alzheimer's disease in Chinese.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Molecular genetic and pathologic studies of Alzheimer's disease in Chinese./
作者:
Chen, Lan.
面頁冊數:
167 p.
附註:
Source: Dissertation Abstracts International, Volume: 60-11, Section: B, page: 5323.
Contained By:
Dissertation Abstracts International60-11B.
標題:
Genetics. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9951504
ISBN:
9780599553736
Molecular genetic and pathologic studies of Alzheimer's disease in Chinese.
Chen, Lan.
Molecular genetic and pathologic studies of Alzheimer's disease in Chinese.
- 167 p.
Source: Dissertation Abstracts International, Volume: 60-11, Section: B, page: 5323.
Thesis (Ph.D.)--The Chinese University of Hong Kong (Hong Kong), 1999.
This item must not be sold to any third party vendors.
Besides the finding of apolipoprotein E (ApoE, gene; ApoE, protein) 3 4 as a strong risk, factor in late onset Alzheimer's disease (AD), polymorphisms in genes for very low density lipoprotein receptor ( VLDLR, gene; VLDLR, protein), low density lipoprotein receptor related protein (LRP, gene; LRP, protein), alpha2-macroglobulin (A2M, gene; A2M, protein) and in the promoter region of ApoE have recently been reported to render genetic susceptibility for AD in Caucasians or Japanese. These genes might be involved in the pathogenesis of AD by affecting beta-amyloid (Abeta) deposition and neurofibrillary tangles (NFT) formation in the brain. In contrast to the vast amount of data in western countries, molecular genetic and pathological studies in Chinese are rare.
ISBN: 9780599553736Subjects--Topical Terms:
530508
Genetics.
Molecular genetic and pathologic studies of Alzheimer's disease in Chinese.
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Source: Dissertation Abstracts International, Volume: 60-11, Section: B, page: 5323.
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Adviser: H. K. Ng.
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Thesis (Ph.D.)--The Chinese University of Hong Kong (Hong Kong), 1999.
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Besides the finding of apolipoprotein E (ApoE, gene; ApoE, protein) 3 4 as a strong risk, factor in late onset Alzheimer's disease (AD), polymorphisms in genes for very low density lipoprotein receptor ( VLDLR, gene; VLDLR, protein), low density lipoprotein receptor related protein (LRP, gene; LRP, protein), alpha2-macroglobulin (A2M, gene; A2M, protein) and in the promoter region of ApoE have recently been reported to render genetic susceptibility for AD in Caucasians or Japanese. These genes might be involved in the pathogenesis of AD by affecting beta-amyloid (Abeta) deposition and neurofibrillary tangles (NFT) formation in the brain. In contrast to the vast amount of data in western countries, molecular genetic and pathological studies in Chinese are rare.
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In this project, I investigated gene polymorphisms in relation to the risk of AD, and ApoE genotype in relation to AD pathology, in a case control study of pathologically and clinically diagnosed sporadic late onset AD (total 226) and age-matched control (total 180) Chinese subjects.
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The polymorphisms I examined included a CGG repeat polymorphism in the 5' untranslated region of VLDLR, a C/T substitution at 766 of LRP exon 3, a 5 base pair deletion near the splicing site of A2M exon 18, three alleles of ApoE exon 4 and a --491 A/T polymorphism in the ApoE promoter region. The ApoE genotype was also studied in relation to Abeta deposition in plaques and NFT in pathologically diagnosed AD patients.
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The results show that ApoE 3 4 is significantly increased in pathologically diagnosed definite or probable AD as compared to controls (chi2, p = 0.00005), and 3 4 is associated with increased Abeta deposition (Mann-Whitney, p = 0.014) but not NFT density in the neocortex of patients. A borderline group of pathologically diagnosed possible AD was also observed to have an increased 3 4 allele frequency (chi2, p = 0.000005) and demonstrated a trend (not statistically significant) toward increased Abeta deposition in the neocortex of 3 4 carriers. The LRP T allele is significantly decreased in pathologically diagnosed (chi2, p = 0.03) but not in clinically diagnosed samples, suggesting it might be protective against AD in Chinese. Polymorphisms in VLDLR, A2M and ApoE promoter are not associated with AD risk in Chinese.
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In conclusion, ApoE 3 4 is a high risk factor for AD in Chinese and might affect Abeta deposition. The association of the LRP exon 3 polymorphism has now been demonstrated in two ethnic groups, Caucasians and Chinese, suggesting LRP is an AD candidate gene. Genetic variation in different ethnicities might mask the risk of polymorphisms in VLDLR, ApoE promoter and A2M in Chinese. (Abstract shortened by UMI.).
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