Multiple SNPs within and surrounding the apolipoprotein E gene influence cerebrospinal fluid apolipoprotein E protein levels

Lynn M. Bekris, Steven P. Millard, Nichole M. Galloway, Simona Vuletic, John J. Albers, Ge Li, Douglas R. Galasko, Charles DeCarli, Martin R. Farlow, Chris M. Clark, Joseph Quinn, Jeffrey Kaye, Gerard D. Schellenberg, Debby Tsuang, Elaine R. Peskind, Chang En Yu

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The ε4 allele of the apolipoprotein E gene (APOE) is associated with increased risk and earlier age at onset in late onset Alzheimer's disease (AD). Other factors, such as expression level of apolipoprotein E protein (apoE), have been postulated to modify the APOE related risk of developing AD. Multiple loci in and outside of APOE are associated with a high risk of AD. The aim of this exploratory hypothesis generating investigation was to determine if some of these loci predict cerebrospinal fluid (CSF) apoE levels in healthy non-demented subjects. CSF apoE levels were measured from healthy non-demented subjects 21-87 years of age (n=134). Backward regression models were used to evaluate the influence of 21 SNPs, within and surrounding APOE, on CSF apoE levels while taking into account age, gender, APOE ε4 and correlation between SNPs (linkage disequilibrium). APOE ε4 genotype does not predict CSF apoE levels. Three SNPs within the TOMM40 gene, one APOE promoter SNP and two SNPs within distal APOE enhancer elements (ME1 and BCR) predict CSF apoE levels. Further investigation of the genetic influence of these loci on apoE expression levels in the central nervous system is likely to provide new insight into apoE regulation as well as AD pathogenesis.

Original languageEnglish (US)
Pages (from-to)255-266
Number of pages12
JournalJournal of Alzheimer's Disease
Volume13
Issue number3
StatePublished - 2008

Fingerprint

Apolipoproteins E
Single Nucleotide Polymorphism
Cerebrospinal Fluid
Genes
Proteins
Apolipoprotein E4
Alzheimer Disease
Genetic Loci
Linkage Disequilibrium
Age of Onset
Central Nervous System
Alleles
Genotype

Keywords

  • Apolipoprotein E gene
  • Apolipoprotein E protein
  • Cerebroshinal fluid
  • Enhancer
  • Promoter
  • SNP

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology

Cite this

Bekris, L. M., Millard, S. P., Galloway, N. M., Vuletic, S., Albers, J. J., Li, G., ... Yu, C. E. (2008). Multiple SNPs within and surrounding the apolipoprotein E gene influence cerebrospinal fluid apolipoprotein E protein levels. Journal of Alzheimer's Disease, 13(3), 255-266.

Multiple SNPs within and surrounding the apolipoprotein E gene influence cerebrospinal fluid apolipoprotein E protein levels. / Bekris, Lynn M.; Millard, Steven P.; Galloway, Nichole M.; Vuletic, Simona; Albers, John J.; Li, Ge; Galasko, Douglas R.; DeCarli, Charles; Farlow, Martin R.; Clark, Chris M.; Quinn, Joseph; Kaye, Jeffrey; Schellenberg, Gerard D.; Tsuang, Debby; Peskind, Elaine R.; Yu, Chang En.

In: Journal of Alzheimer's Disease, Vol. 13, No. 3, 2008, p. 255-266.

Research output: Contribution to journalArticle

Bekris, LM, Millard, SP, Galloway, NM, Vuletic, S, Albers, JJ, Li, G, Galasko, DR, DeCarli, C, Farlow, MR, Clark, CM, Quinn, J, Kaye, J, Schellenberg, GD, Tsuang, D, Peskind, ER & Yu, CE 2008, 'Multiple SNPs within and surrounding the apolipoprotein E gene influence cerebrospinal fluid apolipoprotein E protein levels', Journal of Alzheimer's Disease, vol. 13, no. 3, pp. 255-266.
Bekris, Lynn M. ; Millard, Steven P. ; Galloway, Nichole M. ; Vuletic, Simona ; Albers, John J. ; Li, Ge ; Galasko, Douglas R. ; DeCarli, Charles ; Farlow, Martin R. ; Clark, Chris M. ; Quinn, Joseph ; Kaye, Jeffrey ; Schellenberg, Gerard D. ; Tsuang, Debby ; Peskind, Elaine R. ; Yu, Chang En. / Multiple SNPs within and surrounding the apolipoprotein E gene influence cerebrospinal fluid apolipoprotein E protein levels. In: Journal of Alzheimer's Disease. 2008 ; Vol. 13, No. 3. pp. 255-266.
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abstract = "The ε4 allele of the apolipoprotein E gene (APOE) is associated with increased risk and earlier age at onset in late onset Alzheimer's disease (AD). Other factors, such as expression level of apolipoprotein E protein (apoE), have been postulated to modify the APOE related risk of developing AD. Multiple loci in and outside of APOE are associated with a high risk of AD. The aim of this exploratory hypothesis generating investigation was to determine if some of these loci predict cerebrospinal fluid (CSF) apoE levels in healthy non-demented subjects. CSF apoE levels were measured from healthy non-demented subjects 21-87 years of age (n=134). Backward regression models were used to evaluate the influence of 21 SNPs, within and surrounding APOE, on CSF apoE levels while taking into account age, gender, APOE ε4 and correlation between SNPs (linkage disequilibrium). APOE ε4 genotype does not predict CSF apoE levels. Three SNPs within the TOMM40 gene, one APOE promoter SNP and two SNPs within distal APOE enhancer elements (ME1 and BCR) predict CSF apoE levels. Further investigation of the genetic influence of these loci on apoE expression levels in the central nervous system is likely to provide new insight into apoE regulation as well as AD pathogenesis.",
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AU - Bekris, Lynn M.

AU - Millard, Steven P.

AU - Galloway, Nichole M.

AU - Vuletic, Simona

AU - Albers, John J.

AU - Li, Ge

AU - Galasko, Douglas R.

AU - DeCarli, Charles

AU - Farlow, Martin R.

AU - Clark, Chris M.

AU - Quinn, Joseph

AU - Kaye, Jeffrey

AU - Schellenberg, Gerard D.

AU - Tsuang, Debby

AU - Peskind, Elaine R.

AU - Yu, Chang En

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