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Cited by 85Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchGenetic Associations and Epidemiology

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

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Bekris, Lynn M., Millard, Steven P., Galloway, Nichole M., Vuletic, Simona, Albers, John J., Li, Ge, Galasko, Douglas R., DeCarli, Charles +8 more·2008·Journal of Alzheimer's Disease
DOI 10.3233/jad-2008-13303PMC PMC3192652
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Abstract

The epsilon4 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 epsilon4 and correlation between SNPs (linkage disequilibrium). APOE epsilon4 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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  • More recent studies also report that CSF apoE concentrations, measured by apoE ELISA and nephelometry, do not significantly differ among subjects with different apoE isoforms.

    “More recent studies also report that CSF apoE concentrations, measured by apoE ELISA and nephelometry, do not significantly differ among subjects with different apoE isoforms (Bekris et al., 2008; Wahrle et al., 2007).”

    From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Bekris et al., 2008

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Authors
Bekris, L. M., Millard, S. P., Galloway, N. M., Vuletic, S., Albers, J. J., Li, G., Galasko, D. R., DeCarli, C., Farlow, M. R., Clark, C. M., Quinn, J. F., Kaye, J. A., Schellenberg, G. D., Tsuang, D., Peskind, E. R., & Yu, C.-E.
Affiliations
  • University of Washington (US)
  • VA Puget Sound Health Care System (US)
  • University of California San Diego (US)
  • University of California, Davis (US)
  • Indiana University School of Medicine (US)
  • University of Pennsylvania (US)
  • Oregon Health & Science University (US)
ORCID
Venue
Journal of Alzheimer's Disease
Publisher
SAGE Publications
Published
2008-04-14
Volume
13
Issue
3
Pages
255-266
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-2008-13303
PMC
PMC3192652
OpenAlex
W1648176606
Cited by
85
References
6
Citations by year
2026: 3 · 2024: 3 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 1 · 2018: 6 · 2017: 6 · 2016: 4 · 2015: 5 · 2014: 3 · 2013: 5 · 2012: 10
FWCI
5.33
Type
journal article
Language
en
Open access
Locations
  • Journal of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
Funders
  • U.S. Department of Veterans Affairs (VISN 20)
  • Alzheimer's Association
  • Intel Corporation
  • GlaxoSmithKline
  • Sanofi
  • Eisai
  • National Institutes of Health (AG05136, AG‐08017)
  • National Institute on Aging (P30AG010129, AG 08017, AG 05136, T32AG000258, R21 AG24486-01, U01AG016976, P30AG008017, R21AG024486, P50AG005136)
  • National Heart, Lung, and Blood Institute (P01HL030086)
  • National Institute of Neurological Disorders and Stroke (R01NS048595)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
apolipoprotein E, APOE gene
MeSH terms
Mitochondrial Precursor Protein Import Complex Proteins, Adult, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Enhancer Elements, Genetic, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Promoter Regions, Genetic, Severity of Illness Index, Linkage Disequilibrium, DNA Primers, Polymorphism, Single Nucleotide, Membrane Transport Proteins, Apolipoprotein E4

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