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Table of Contents
Vol. 17, No. 1, 1998
Issue release date: January–February 1998
Neuroepidemiology 1998;17:14–20
(DOI:10.1159/000026149)

Serum Total Cholesterol, Apolipoprotein E {FC12}e4 Allele, and Alzheimer’s Disease

Notkola I.-L. · Sulkava R. · Pekkanen J. · Erkinjuntti T. · Ehnholm C. · Kivinen P. · Tuomilehto J. · Nissinen A.
a Department of Public Health and General Practice, University of Kuopio, Departments of b Environmental Medicine, c Biochemistry, and d Epidemiology and Health Promotion, National Public Health Institute, Helsinki, e Department of Neurology, University of Helsinki, Finland

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Abstract

The σ4 allele of the apolipoprotein E (apoE) is associated with Alzheimer’s disease (AD) and also with elevated serum total cholesterol and low-density lipoprotein levels. However, the interrelationships between apoE genotype, plasma cholesterol levels and AD risk have been studied very little. We examined the possible role of serum total cholesterol in the pathogenesis of AD in a population-based sample of 444 men, aged 70–89 years, who were survivors of the Finnish cohorts of the Seven Countries Study. Previous high serum cholesterol level (mean level ≥6.5 mmol/l) was a significant predictor of the prevalence of AD (odds ratio = 3.1; 95% confidence interval = 1.2, 8.5) after controlling for age and the presence of apoE σ4 allele. In men who subsequently developed AD the cholesterol level decreased before the clinical manifestations of AD. We conclude that high serum total cholesterol may be an independent risk factor for AD and some of the effect of the apoE σ4 allele on risk of AD might be mediated through high serum cholesterol.



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References

  1. Mahley RW: Apolipoprotein E: Cholesterol transport protein with expanding role in cell biology. Science 1988;240:622–630.
  2. Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance, M, Enghild J, Salvesen GS, Roses AD: Apolipoprotein E: High-activity binding to β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 1993;90:1977–1981.
  3. Stengård 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.
  4. Schmechel DE, Saunders AM, Strittmatter WJ, Crain BJ, Hulette CM, Joo SH, Pericak-Vance MA, Goldgaber D, Roses AD: Increased amyloid β-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci USA 1993;90:9649–9653.
  5. Polvikoski T, Sulkava R, Haltia M, Kainulainen K, Vuorio A, Verkkoniemi A, Niinistö L, Halonen P, Kontula K: Apolipoprotein E, dementia, and cortical deposition of β-amyloid protein. N Engl J Med 1995;333:1242–1247.
  6. Roses AD: Apolipoprotein E affects the rate of Alzheimer disease expression: β-Amyloid burden is a secondary consequence dependent on APOE genotype and duration of disease. J Neuropathol Exp Neurol 1994;53:429–437.
  7. Davignon J, Gregg RE, Sing CF: Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 1988;8:1–21.
  8. Jarvik GP, Wijsman EM, Kukull WA, Schellenberg GD, Yu C, Larson EB: Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer’s disease: A case-control study. Neurology 1995;45:1092–1096.
  9. Keys A: Coronary Heart Disease in Seven Countries. New York, American Heart Association Monograph, 1970.
  10. Folstein MF, Folstein SE, McHugh PR: ‘Mini-Mental State’: A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198.
  11. Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL: A new clinical scale for the staging of dementia. Br J Psychiatry 1982;140:566–572.
  12. American Psychiatric Association: Diagnostic and statistical manual of mental disorders, ed 3 revised (DSM-III-R). Washington, American Psychiatric Association, 1987.
  13. Blessed G, Tomlinson BE, Roth M: The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 1968;114:797–811.
  14. Sulkava R, Haltia M, Paetau A, Wikström J, Palo J: Accuracy of clinical diagnosis in primary degenerative dementia: Correlation with neuropathological findings. J Neurol Neurosurg Psychiatry 1983;46:9–13.

    External Resources

  15. Pfeiffer E: A short portable mental status questionnaire for the assessment of organic brain deficit in elderly patients. J Am Geriatr Soc 1975;23:433–441.
  16. Abell L, Levy B, Brodie B, Kendall F: A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J Biol Chem 1952;195:357–366.
  17. Anderson JT, Keys A: Cholesterol in serum and lipoprotein fractions: Its measurement and stability. Clin Chem 1956;2:145–159.
  18. Röschlau P, Bernt E, Gruber W: Enzymatische Bestimmung des Gesamtcholesterins im Serum. Z Clin Chem Biochem 1974;12:403–407.
  19. Pekkanen J, Nissinen A, Vartiainen E, Salonen JT, Punsar S, Karvonen MJ: Changes in serum cholesterol level and mortality: A 30-year follow-up. The Finnish cohorts of the Seven Countries Study. Am J Epidemiol 1994;139:155–165.

    External Resources

  20. Ehnholm C, Lukka M, Kuusi T, Nikkilä E, Utermann G: Apolipoprotein E polymorphism in the Finnish population: Gene frequencies and relation to lipoprotein concentrations. J Lipid Res 1986;27:227–235.
  21. Havekes LM, de Knijff P, Beisiegel U, Havinga J, Smit M, Klasen E: A rapid micromethod for apolipoprotein E phenotyping directly in serum. J Lipid Res 1987;28:455–463.

    External Resources

  22. Lahoz C, Osgood D, Wilson PWF, Schaefer EJ, Ordovas JM: Frequency of phenotype-genotype discrepancies at the apolipoprotein E locus in a large population study. Clin Chem 1996;42:1817–1823.
  23. Martin MJ, Hulley SB, Browner WS, Kuller LH, Wentworth D: Serum cholesterol, blood pressure, and mortality: Implications from a cohort of 361 662 men. Lancet 1986;ii:933–936.
  24. Hallman DM, Boerwinkle E, Saha N, Sandholzer C, Menzel HJ, Csázár A, Utermann G: The apolipoprotein E polymorphism: A comparison of allele frequencies and effects in nine populations. Am J Hum Genet 1991;49:338–349.
  25. Henderson AS: Dementia. Geneva, World Health Organization, 1994.
  26. Hofman A, Ott A, Breteler MMB, Bots ML, Slooter AJC, van Harskamp F, van Duijn CN, van Broeckhoven C, Grobbee DE: Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer’s disease in the Rotterdam study. Lancet 1997;349:151–154.
  27. Sparks DL, Liu H, Scheff SW, Coyne CM, Hunsaker JC III: Temporal sequence of plaque formation in the cerebral cortex of non-demented individuals. J Neuropathol Exp Neurol 1993;52:135–142.

    External Resources

  28. Sparks DL, Scheff SW, Hunsaker JC III, Liu H, Landers T, Gross DR: Induction of Alzheimer-like beta-amyloid immunoreactivity in the brains of rabbits with dietary cholesterol. Exp Neurol 1994;126:88–94.
  29. Henderson AS, Easteal S, Jorm AF, Mackinnon AJ, Korten AE, Christensen H, Croft L, Jacomb PA: Apolipoprotein E allele σ4, dementia, and cognitive decline in a population sample. Lancet 1995;346:1387–1390.
  30. Susser M: Causal thinking in the health sciences. New York, Oxford University Press, 1973.
  31. Sephernia B, Kamboh MI, Adams-Campbell LL, Nwankwo M, Ferrell RE: Genetic studies of human apolipoproteins. VII. Population distribution of polymorphisms of apolipoproteins A-I, A-II, A-IV, C-II, E, and H in Nigeria. Am J Hum Genet 1988;43:847–853.
  32. Erasmus RT, Uyot C, Pakeye T: Plasma cholesterol distribution in a rural Nigerian population – relationship to age, sex and body mass. Cent Afr J Med 1994;40:299–302.
  33. Hendrie HC, Osuntokun BO, Hall KA, Ogunniyi AO, Hui SL, Unverzagt FW, Gureje O, Rodenberg CA, Baiyewu O, Musick BS, et al: Prevalence of Alzheimer’s disease and dementia in two communities: Nigerian Africans and African Americans. Am J Psychiatry 1995;152:1485–1492.
  34. Sandholzer C, Delport R, Vermaak H, Utermann G: High frequency of the apo σ4 allele in Khoi San from South Africa. Hum Genet 1995;95:46–48.
  35. Osuntokun BO, Sahota A, Ogunniyi AO, Gureje O, Baiyewu O, Adeyinka A, Oluwole SO, Komolafe O, Hall KS, Unverzagt FW, et al: Lack of an association between apolipoprotein E σ4 and Alzheimer’s disease in elderly Nigerians. Ann Neurol 1995;38:463–465.
  36. Hendrie HC, Hall KS, Hui S, Unverzagt FW, Yu CE, Lahiri DK, Sahota A, Farlow M, Musick B, Class CA, et al: Apolipoprotein E genotypes and Alzheimer’s disease in a community study of elderly African Americans. Ann Neurol 1995;37:118–120.
  37. Levine GN, Keaney JF, Vita JA: Cholesterol reduction in cardiovascular disease. Clinical benefits and possible mechanisms. N Engl J Med 1995;332:512–521.
  38. Thomas T, Thomas G, McLendon C, Sutton T, Mullan M: Beta-amyloid-mediated vasoactivity and vascular endothelial damage. Nature 1996;380:168–171.
  39. Bodovitz S, Klein WL: Cholesterol modulates α-secretase cleavage of amyloid precursor protein. J Biol Chem 1996;271:4436–4440.
  40. Araki W, Kitaguchi N, Tokushima Y, Ishii K, Aratake H, Shimohama S, Nakamura S, Kimura J: Trophic effect of beta-amyloid precursor protein on cerebral cortical neurons in culture. Biochem Biophys Res Commun 1991;181:265–271.

    External Resources

  41. Mattson MP, Cheng B, Culwell AR, Esch FS, Lieberburg I, Rydel RE: Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the beta-amyloid precursors protein. Neuron 1993;10:243–254.
  42. Ettinger WH Jr, Harris T: Causes of hypocholesterolemia. Coron Artery Dis 1993;4:854–859.
  43. Skoog I, Lernfelt B, Landahl S, Palmertz B, Andreasson L-A, Nilsson L, Persson G, Oden A, Svanborg A: 15-year longitudinal study of blood pressure and dementia. Lancet 1996;347:1141–1145.
  44. Erkinjuntti T, Sulkava R, Tilvis R: Plasma lipids in Alzheimer’s disease and vascular dementia. Proc 8th Scand Congr Gerontol, Tampere, May 25–28, 1986, pp 499–502.


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