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Cited by 63Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

APOE ε3/ε4 heterozygotes have an elevated proportion of apolipoprotein E4 in cerebrospinal fluid relative to plasma, independent of Alzheimer’s disease diagnosis

Fukumoto, Hiroaki, Ingelsson, Martin, Gårevik, Nina, Wahlund, Lars-Olof, Nukina, Nobuyuki, Yaguchi, Yoshio, Shibata, Masao, Hyman, Bradley T. +2 more·2003·Experimental Neurology
DOI 10.1016/s0014-4886(03)00088-8
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Abstract

Inheritance of the apolipoprotein E (APOE) epsilon 4 allele is associated with an increased risk of Alzheimer's disease (AD). However, the risk of AD in APOE epsilon 3/ epsilon 4 heterozygotes is variable. We tested the hypothesis that the risk of AD in APOE epsilon 3/ epsilon 4 heterozygotes was linked to the relative levels of expression of apoE4 versus apoE3 protein. We measured the apoE4 isoform and total apoE using two specific enzyme-linked immunosorbent assay (ELISA) kits in three cohorts of plasma samples and two cohorts of cerebrospinal fluid samples from AD, mild cognitive impairment, and control subjects. The apoE4 ELISAs were specific as they did not detect apoE in APOE epsilon 3/epsilon 3 homozygotes and were comparable to the total apoE ELISAs in APOE epsilon 4/ epsilon 4 homozygotes. In APOE epsilon 3/ epsilon 4 individuals, the ratio of apoE4 to total apoE levels was 30-40% in plasma, suggesting a decreased production or an increased metabolism of apoE4 compared to apoE3. Surprisingly, the ratio in the CSF was reversed, with apoE4 accounting for 60-70% of the total apoE. The proportion of apoE4 in these cases did not vary by diagnosis, age of onset, or duration of AD. We conclude that the proportion of apoE4 in plasma is not predictive of AD risk in APOE epsilon 3/epsilon 4 individuals. However, the greater proportion of apoE4 in the cerebrospinal fluid suggests differential production or metabolism of the protein in the central nervous system (CNS), with the…

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  • One study reported that apoE4 accounted for 60-70% of the total apoE protein in CSF from ε3/ε4 heterozygote subjects, which contrasted with the lower proportion of apoE4 in plasma.

    “One study reported that apoE4 accounted for 60–70% of the total apoE protein in CSF from ε3/ε4 heterozygote subjects, which contrasted with the lower proportion of apoE4 in plasma (Fukumoto et al., 2003).”

    From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Fukumoto et al., 2003

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Authors
Fukumoto, H., Ingelsson, M., Gårevik, N., Wahlund, L.-O., Nukina, N., Yaguchi, Y., Shibata, M., Hyman, B. T., Rebeck, G. W., & Irizarry, M. C.
Affiliations
  • Massachusetts General Hospital (US)
  • Karolinska Institutet (SE)
  • RIKEN Center for Brain Science (JP)
  • Medical & Biological Laboratories (Japan) (JP)
Corresponding author
Irizarry, Michael C.
ORCID
Venue
Experimental Neurology
Publisher
Elsevier BV
Published
2003-09
Volume
183
Issue
1
Pages
249-253
ISSN
0014-4886 (ISSN-L)
DOI
10.1016/s0014-4886(03)00088-8
OpenAlex
W2060911735
Cited by
63
References
6
Citations by year
2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2020: 2 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 6 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 5
FWCI
2.55
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (P50AG005134, AG00793, AG 05134)
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 › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
apolipoprotein E, APOE ε4, cerebrospinal fluid, plasma, Alzheimer's disease risk, mild cognitive impairment, central nervous system, biomarkers
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Female, Genotype, Heterozygote, Humans, Male, Massachusetts, Predictive Value of Tests, Reference Values, Risk, Sweden, Cohort Studies, Age of Onset, Apolipoprotein E3, Apolipoprotein E4

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