Is There a Relation Between APOE Expression and Brain Amyloid Load in Alzheimer's Disease?

Overview

Journal J Neurol Neurosurg Psychiatry

Publisher BMJ Publishing Group

Specialties Neurology
Neurosurgery
Psychiatry

Date 2005 Jun 21

PMID 15965197

Citations 25

Authors

J-C Lambert

D Mann

F Richard

J Tian

J Shi

U Thaker

S Merrot

J Harris

B Frigard

T Iwatsubo

C Lendon

P Amouyel

Affiliations

Soon will be listed here.

Abstract

Background: It has been proposed that, independent of the epsilon4 allele, APOE promoter polymorphisms (-491 A/T and -219 G/T) may be risks factor for Alzheimer's disease by modulating APOE expression.

Objective: To measure the level of APOE expression in Alzheimer's disease.

Methods: Brains were obtained at necropsy from 114 patients with early and late onset sporadic Alzheimer's disease in Greater Manchester (UK) during years 1986 to 2001. Total RNA was extracted from 84 brains. Purified lymphocytes were obtained from fresh blood from 16 probable Alzheimer cases from Lille (France). APOE and beta-actin gene expression was determined by reverse transcriptase polymerase chain reaction in brain and lymphocytes.

Results: An inverse correlation between APOE expression level and A beta loads was observed. As previously described and extended to 114 cases here, an association between the -219 TT genotype and a higher level of parenchymal A beta deposition was found, irrespective of APOE epsilon4 allele status. This effect was more pronounced in older individuals, whereas higher A beta load appeared more closely related to epsilon4 in the younger age group (cut off point at the median age at death (72.5 years)). The -219 TT genotype was associated with a decrease in APOE expression. There was a 60% decrease in APOE expression in lymphocytes from probable Alzheimer cases v controls (p = 0.01).

Conclusions: In the oldest individuals, reduced APOE expression, modulated in part by -219 G/T polymorphism, may influence risk and constitute a determinant A beta load in Alzheimer's disease.

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References

Hesse C, Bogdanovic N, Davidsson P, Blennow K . A quantitative and immunohistochemical study on apolipoprotein E in brain tissue in Alzheimer's disease. Dement Geriatr Cogn Disord. 1999; 10(6):452-9. DOI: 10.1159/000017189. View

Lambert J, Brousseau T, Defosse V, Evans A, Arveiler D, Ruidavets J . Independent association of an APOE gene promoter polymorphism with increased risk of myocardial infarction and decreased APOE plasma concentrations-the ECTIM study. Hum Mol Genet. 1999; 9(1):57-61. DOI: 10.1093/hmg/9.1.57. View

Ramassamy C, Averill D, Beffert U, Theroux L, Cohn J, Christen Y . Oxidative insults are associated with apolipoprotein E genotype in Alzheimer's disease brain. Neurobiol Dis. 2000; 7(1):23-37. DOI: 10.1006/nbdi.1999.0273. View

Fukuyama R, Mizuno T, Mori S, Yanagisawa K, Nakajima K, Fushiki S . Age-dependent decline in the apolipoprotein E level in cerebrospinal fluid from control subjects and its increase in cerebrospinal fluid from patients with Alzheimer's disease. Eur Neurol. 2000; 43(3):161-9. DOI: 10.1159/000008157. View

Hesse C, Larsson H, Fredman P, Minthon L, Andreasen N, Davidsson P . Measurement of apolipoprotein E (apoE) in cerebrospinal fluid. Neurochem Res. 2000; 25(4):511-7. DOI: 10.1023/a:1007516210548. View

Zurutuza L, Verpillat P, Raux G, Hannequin D, Puel M, Belliard S . APOE promoter polymorphisms do not confer independent risk for Alzheimer's disease in a French population. Eur J Hum Genet. 2000; 8(9):713-6. DOI: 10.1038/sj.ejhg.5200513. View

Berr C, Lambert J, Sazdovitch V, Amouyel P, Chartier-Harlin M, Mohr M . Neuropathological epidemiology of cerebral aging: a study of two genetic polymorphisms. Neurobiol Aging. 2001; 22(2):227-35. DOI: 10.1016/s0197-4580(00)00227-x. View

Yamagata K, Urakami K, Ikeda K, Ji Y, Adachi Y, Arai H . High expression of apolipoprotein E mRNA in the brains with sporadic Alzheimer's disease. Dement Geriatr Cogn Disord. 2001; 12(2):57-62. DOI: 10.1159/000051236. View

Perry R, Collins J, Harrell L, Acton R, Go R . Investigation of association of 13 polymorphisms in eight genes in southeastern African American Alzheimer disease patients as compared to age-matched controls. Am J Med Genet. 2001; 105(4):332-42. DOI: 10.1002/ajmg.1371. View

10.

Lambert J, Mann D, Goumidi L, Harris J, Amouyel P, Iwatsubo T . Effect of the APOE promoter polymorphisms on cerebral amyloid peptide deposition in Alzheimer's disease. Lancet. 2001; 357(9256):608-9. DOI: 10.1016/S0140-6736(00)04063-0. View

11.

Holtzman D . Role of apoe/Abeta interactions in the pathogenesis of Alzheimer's disease and cerebral amyloid angiopathy. J Mol Neurosci. 2002; 17(2):147-55. DOI: 10.1385/JMN:17:2:147. View

12.

Heijmans B, Slagboom P, Gussekloo J, Droog S, Lagaay A, Kluft C . Association of APOE epsilon2/epsilon3/epsilon4 and promoter gene variants with dementia but not cardiovascular mortality in old age. Am J Med Genet. 2002; 107(3):201-8. DOI: 10.1002/ajmg.10142. View

13.

Viitanen L, Pihlajamaki J, Miettinen R, Karkkainen P, Vauhkonen I, Halonen P . Apolipoprotein E gene promoter (-219G/T) polymorphism is associated with premature coronary heart disease. J Mol Med (Berl). 2002; 79(12):732-7. DOI: 10.1007/s001090100265. View

14.

Myllykangas L, Polvikoski T, Reunanen K, Wavrant-De Vrieze F, Ellis C, Hernandez D . ApoE epsilon3-haplotype modulates Alzheimer beta-amyloid deposition in the brain. Am J Med Genet. 2002; 114(3):288-91. DOI: 10.1002/ajmg.10202. View

15.

Lambert J, Araria-Goumidi L, Myllykangas L, Ellis C, Wang J, Bullido M . Contribution of APOE promoter polymorphisms to Alzheimer's disease risk. Neurology. 2002; 59(1):59-66. DOI: 10.1212/wnl.59.1.59. View

16.

Roks G, Cruts M, Houwing-Duistermaat J, Dermaut B, Serneels S, Havekes L . Effect of the APOE-491A/T promoter polymorphism on apolipoprotein E levels and risk of Alzheimer disease: The Rotterdam Study. Am J Med Genet. 2002; 114(5):570-3. DOI: 10.1002/ajmg.10407. View

17.

Laws S, Hone E, Taddei K, Harper C, Dean B, McClean C . Variation at the APOE -491 promoter locus is associated with altered brain levels of apolipoprotein E. Mol Psychiatry. 2002; 7(8):886-90. DOI: 10.1038/sj.mp.4001097. View

18.

Pahnke J, Walker L, Schroeder E, Vogelgesang S, Stausske D, Walther R . Cerebral beta-amyloid deposition is augmented by the -491AA promoter polymorphism in non-demented elderly individuals bearing the apolipoprotein E epsilon4 allele. Acta Neuropathol. 2002; 105(1):25-9. DOI: 10.1007/s00401-002-0602-0. View

19.

Thaker U, McDonagh A, Iwatsubo T, Lendon C, Pickering-Brown S, Mann D . Tau load is associated with apolipoprotein E genotype and the amount of amyloid beta protein, Abeta40, in sporadic and familial Alzheimer's disease. Neuropathol Appl Neurobiol. 2003; 29(1):35-44. DOI: 10.1046/j.1365-2990.2003.00425.x. View

20.

Nathan B, Bellosta S, Sanan D, Weisgraber K, Mahley R, Pitas R . Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro. Science. 1994; 264(5160):850-2. DOI: 10.1126/science.8171342. View