Journal Mobile Options
Table of Contents
Vol. 23, No. 3, 2004
Issue release date: May–June 2004
Neuroepidemiology 2004;23:129–134

Apolipoprotein E Polymorphism in Ischemic Cerebrovascular Diseases and Vascular Dementia Patients in Taiwan

Lin H.-F. · Lai C.-L. · Tai C.-T. · Lin R.-T. · Liu C.-K.
Department of Neurology, Kaohsiung Medical University, Kaohsiung City, Taiwan, ROC

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


This study aims to clarify the association between apolipoprotein E gene (ApoE) polymorphism, ischemic cerebrovascular diseases (ICVD) and vascular dementia (VaD) in Taiwan Chinese. 277 patients with ICVD, 49 patients with probable VaD and 112 controls were recruited for this study. Distributions of ApoE ε4 carriers and allele frequencies were 28.5 and 14.5% for patients with ICVD, 20.4 and 10.2% for patients with VaD, whereas these values were 22.9 and 11.6% for controls. Distributions of ApoE ε2 carriers and allele frequencies were 10.1 and 5.2% for ICVD patients, 6.1 and 3.1% for VaD patients, but 12.5 and 8.0% for controls. There were no differences between ICVD patients and controls, or VaD patients and controls in their ε4 carriers. Those patients aged 65 and under, carrying the ε2 allele, had a lower risk of developing ICVD and VaD than did their counterparts. These findings suggest that ApoE ε4 plays no significant role in the development of ICVD and VaD, but that ApoE ε2 has a protective effect with regard to the development of ICVD and VaD for Taiwan Chinese below the age of 65.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Davignon J, Gregg RE, Sing CF: Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 1988;8:1–21.
  2. Nathan BP, Bellosta S, Sanan DA, Weisgraber KH, Mahley RW, Pitas RE: Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro. Science 1994;264:850–852.
  3. Dickson DW, Roy N, Graff-Radford D, et al: Apolipoprotein-E genotype influences amyloid deposition and limbic neurofibrillary degeneration, but not Lewy body or vascular pathologies in postmortem brains. Neurology 1999;52:A562–A563.
  4. Hixson JE: Apolipoprotein E polymorphisms affect atherosclerosis in young males. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb 1991;11:1237–1244.
  5. Cattin L, Fisicaro M, Tonizzo M, et al: Polymorphism of the apolipoprotein E gene and early carotid atherosclerosis defined by ultrasonography in asymptomatic adults. Arterioscler Thromb Vasc Biol 1997;17:91–94.
  6. Wilson PW, Schaefer EJ, Larson MG, Ordovas JM: Apolipoprotein E alleles and risk of coronary disease. A meta-analysis. Arterioscler Thromb Vasc Biol 1996;16:1250–1255.
  7. Katzel LI, Fleg JL, Paidi M, Ragoobarsingh N, Goldberg AP: ApoE4 polymorphism increases the risk for exercise-induced silent myocardial ischemia in older men. Arterioscler Thromb 1993;13:1495–1500.
  8. Kuusisto J, Koivisto K, Kervinen K, et al: Association of apolipoprotein E phenotypes with late onset Alzheimer’s disease: Population based study. BMJ 1994;309:636–638.
  9. Treves TA, Bornstein NM, Chapman J, et al: APOE-epsilon 4 in patients with Alzheimer disease and vascular dementia. Alzheimer Dis Assoc Disord 1996;10:189–191.
  10. Hofman A, Ott A, Breteler MM, et al: Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer’s disease in the Rotterdam Study. Lancet 1997;349:151–154.
  11. Pedro-Botet J, Senti M, Nogues X, et al: Lipoprotein and apolipoprotein profile in men with ischemic stroke: Role of lipoprotein(a), triglyceride-rich lipoproteins, and apolipoprotein E polymorphism. Stroke 1992;23:1556–1562.
  12. Couderc R, Mahieux F, Bailleul S, Fenelon G, Mary R, Fermanian J: Prevalence of apolipoprotein E phenotypes in ischemic cerebrovascular disease: A case-control study. Stroke 1993;24:661–664.
  13. Schmidt R, Schmidt H, Fazekas F, et al: Apolipoprotein E polymorphism and silent microangiopathy-related cerebral damage. Results of the Austrian Stroke Prevention Study. Stroke 1997;28:951–956.
  14. Ji Y, Urakami K, Adachi Y, Maeda M, Isoe K, Nakashima K: Apolipoprotein E polymorphism in patients with Alzheimer’s disease, vascular dementia and ischemic cerebrovascular disease. Dement Geriatr Cogn Disord 1998;9:243–245.
  15. Kuusisto J, Mykkanen L, Kervinen K, Kesaniemi YA, Laakso M: Apolipoprotein E4 phenotype is not an important risk factor for coronary heart disease or stroke in elderly subjects. Arterioscler Thromb Vasc Biol 1995;15:1280–1286.
  16. Zhu L, Fratiglioni L, Guo Z, et al: Incidence of dementia in relation to stroke and the apolipoprotein E epsilon4 allele in the very old: Findings from a population-based longitudinal study. Stroke 2000;31:53–60.
  17. Basun H, Corder EH, Guo Z, et al: Apolipoprotein E polymorphism and stroke in a population sample aged 75 years or more. Stroke 1996;27:1310–1315.
  18. Lin RT, Lai CL, Tai CT, Liu CK, Yen YY, Howng SL: Prevalence and subtypes of dementia in southern Taiwan: Impact of age, sex, education, and urbanization. J Neurol Sci 1998;160:67–75.
  19. Liu CK, Lin RT, Chen YF, Tai CT, Yen YY, Howng SL: Prevalence of dementia in an urban area in Taiwan. J Formos Med Assoc 1996;95:762–768.
  20. De Carli C, Reed T, Miller BL, Wolf PA, Swan GE, Carmelli D: Impact of apolipoprotein E epsilon4 and vascular disease on brain morphology in men from the NHLBI twin study. Stroke 1999;30:1548–1553.
  21. Pirttila T, Lehtimaki T, Rinne J, Mattila K, Frey H, Nikkari T: The frequency of apolipoprotein E4 allele is not increased in patients with probable vascular dementia. Acta Neurol Scand 1996;93:352–354.
  22. Stengard JH, Pekkanen J, Sulkava R, Ehnholm C, Erkinjuntti T, Nissinen A: Apolipoprotein E polymorphism, Alzheimer’s disease and vascular dementia among elderly Finnish men. Acta Neurol Scand 1995;92:297–298.
  23. Nakayama S, Kuzuhara S: Apolipoprotein E phenotypes in healthy normal controls and demented subjects with Alzheimer’s disease and vascular dementia in Mie Prefecture of Japan. Psychiatry Clin Neurosci 1999;53:643–648.
  24. Liu HC, Hong CJ, Wang SJ, et al: ApoE genotype in relation to AD and cholesterol: A study of 2,326 Chinese adults. Neurology 1999;53:962–966.
  25. Kao JT, Tsai KS, Chang CJ, Huang PC: The effects of apolipoprotein E polymorphism on the distribution of lipids and lipoproteins in the Chinese population. Atherosclerosis 1995;114:55–59.
  26. Wenham PR, Price PH, Blundell A: Apolipoprotein E genotyping by one gate PCR. Lancet 1991;337:1158–1159.
  27. Slooter AJ, Bots ML, Havekes LM, et al: Apolipoprotein E and carotid artery atherosclerosis: The Rotterdam study. Stroke 2001;32:1947–1952.
  28. Molero AE, Pino-Ramirez G, Maestre GE: Modulation by age and gender of risk for Alzheimer’s disease and vascular dementia associated with the apolipoprotein E-epsilon4 allele in Latin Americans: Findings from the Maracaibo Aging Study. Neurosci Lett 2001;307: 5–8.
  29. Schachter F, Faure-Delanef L, Guenot F, et al: Genetic associations with human longevity at the Apo E and ACE loci. Nat Genet 1994;6:29–32.
  30. Katzman R, Zhang MY, Chen PJ, et al: Effects of apolipoprotein E on dementia and aging in the Shanghai Survey of Dementia. Neurology 1997;49:779–785.
  31. Yang J, Feng G, Zhang J, et al: Is ApoE gene a risk factor for vascular dementia in Han Chinese? Int J Mol Med 2001;7:217–219.
  32. Zhang JG, Yang JG, Lin ZX, et al: Apolipoprotein E epsilon4 allele is a risk factor for late-onset Alzheimer’s disease and vascular dementia in Han Chinese. Int J Geriatr Psychiatry 2001;16:438–439.
  33. Kawamata J, Tanaka S, Shimohama S, Ueda K, Kimura J: Apolipoprotein E polymorphism in Japanese patients with Alzheimer’s disease or vascular dementia. J Neurol Neurosurg Psychiatry 1994;57:1414–1416.
  34. Higuchi S, Arai H, Nakagawa T, Muramatsu T, Sasaki H, Trojanowski JQ: The apolipoprotein E gene in Binswanger’s disease and vascular dementia. Clin Genet 1996;50:459–461.
  35. Tang MX, Maestre G, Tsai WY, et al: Effect of age, ethnicity, and head injury on the association between APOE genotypes and Alzheimer’s disease. Ann NY Acad Sci 1996;802:6–15.
  36. Farrer LA, Cupples LA, Haines JL, et al: Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 1997;278:1349–1356.
  37. Reed DM: The paradox of high risk of stroke in populations with low risk of coronary heart disease. Am J Epidemiol 1990;131:579–588.
  38. Liu L, Mizushima S, Ikeda K, et al: Comparative studies of diet-related factors and blood pressure among Chinese and Japanese: Results from the China-Japan Cooperative Research of the WHO-CARDIAC Study – Cardiovascular disease and alimentary comparison. Hypertens Res 2000;23:413–420.
  39. Ueshima H, Zhang XH, Choudhury SR: Epidemiology of hypertension in China and Japan. J Hum Hypertens 2000;14:765–769.
  40. Skoog I, Hesse C, Aevarsson O, et al: A population study of apoE genotype at the age of 85: Relation to dementia, cerebrovascular disease, and mortality. J Neurol Neurosurg Psychiatry 1998;64:37–43.
  41. Bergem AL, Engedal K, Kringlen E: The role of heredity in late-onset Alzheimer disease and vascular dementia: A twin study. Arch Gen Psychiatry 1997;54:264–270.
  42. Gupta SR, Naheedy MH, Young JC, Ghobrial M, Rubino FA, Hindo W: Periventricular white matter changes and dementia: Clinical, neuropsychological, radiological, and pathological correlation. Arch Neurol 1988;45:637–641.
  43. Lin RT, Lai CL, Tai CT, Liu CK, Howng SL: Cranial computed tomography in ischemic stroke patients with and without dementia – A prospective study. Kaohsiung J Med Sci 1998;14:203–211.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50