Plasma apolipoprotein E and Alzheimer disease risk: The AIBL study of aging
Abstract
Objective There is mounting evidence for the contribution of apoE to the pathophysiology of Alzheimer disease (AD). Studies also indicate that plasma apoE levels may reflect disease status, suggesting that apoE is a potential AD biomarker. However, while some studies of apoE levels in plasma have presented correlations with AD pathology, others have not. Thus, there is a lack of consensus as to the suitability of plasma apoE as an AD biomarker. The major objective of this cross-sectional study was to investigate total plasma apoE as well as levels of the apoE4 form in a large, highly characterized cohort which included both healthy controls and participants with early-stage AD. Methods Total apoE and apoE4 were measured in 1,079 individuals drawn from the highly characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Total and isoform-specific plasma apoE levels were then compared with cerebral Aβ load, as assessed by PET using Pittsburgh compound B (PiB). Results Total apoE and apoE4 levels were found to be significantly lower in patients with AD in the entire cohort, and decrease with Aβ load in the PiB-PET subset. ApoE levels were significantly lower among ε4 homozygous individuals. In APOE ε3/ε4 heterozygote carriers, apoE4 levels decrease, indicating that apoE3 levels increase with disease. Conclusion Analysis of cross-sectional data from the AIBL study indicates that plasma apoE levels are altered in AD and correlate with AD pathology level. The signifi…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Earlier association studies of plasma ApoE level with Alzheimer's disease have reported inconsistent findings.
“Earlier association studies of plasma ApoE level with AD have reported inconsistent findings [26–31]”
From Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer’s disease risk (2023) · cites this paper as [26]
Cites
Mild Cognitive Impairment: Clinical Characterization and Outcome
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1999) · Archives of Neurology · doi:10.1001/archneur.56.3.303 · Cited by 8,980 · see citing works
Abnormal in vivo metabolism of apolipoprotein E4 in humans.
Gregg, R. E., Zech, L. A., Schaefer, E. J., Stark, D., Wilson, D., & Brewer, H. B. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112645 · Cited by 345 · see citing works
Impact of Apolipoprotein E (ApoE) Polymorphism on Brain ApoE Levels
Riddell, D. R., Zhou, H., Atchison, K., Warwick, H. K., Atkinson, P. J., Jefferson, J., Xu, L., Aschmies, S., Kirksey, Y., Hu, Y., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1972-08.2008 · Cited by 342 · see citing works
Apolipoprotein E4 Forms a Molten Globule
Morrow, J. A., Hatters, D. M., Lu, B., Höchtl, P., Oberg, K. A., Rupp, B., & Weisgraber, K. H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204898200 · Cited by 204 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.263 · Cited by 3,459 · see citing works
Amyloid-β-independent regulators of tau pathology in Alzheimer disease
van der Kant, R., Goldstein, L. S. B., & Ossenkoppele, R. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0240-3 · Cited by 580 · see citing works
Apolipoprotein E in Alzheimer's Disease: An Update
Yu, J.-T., Tan, L., & Hardy, J. (2014) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071013-014300 · Cited by 394 · see citing works
Weiner, M. W., Veitch, D. P., Aisen, P. S., Beckett, L. A., Cairns, N. J., Cedarbaum, J., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.11.001 · Cited by 348 · see citing works
Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases
Vance, J. E. (2012) · Disease Models & Mechanisms · doi:10.1242/dmm.010124 · Cited by 342 · see citing works
Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease
Cruchaga, C., Kauwe, J. S. K., Nowotny, P., Bales, K., Pickering, E. H., Mayo, K., Bertelsen, S., Hinrichs, A., Fagan, A. M., Holtzman, D. M., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds296 · Cited by 207 · see citing works
Bien-Ly, N., Gillespie, A. K., Walker, D., Yoon, S. Y., & Huang, Y. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0033-12.2012 · Cited by 170 · see citing works
Martínez-Morillo, E., Hansson, O., Atagi, Y., Bu, G., Minthon, L., Diamandis, E. P., & Nielsen, H. M. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1266-2 · Cited by 168 · see citing works
Fowler, C., Rainey-Smith, S. R., Bird, S., Bomke, J., Bourgeat, P., Brown, B. M., Burnham, S. C., Bush, A. I., Chadunow, C., Collins, S., et al. (2021) · Journal of Alzheimer's Disease Reports · doi:10.3233/adr-210005 · Cited by 164 · see citing works
Self-citationATP-binding cassette transporter A1: From metabolism to neurodegeneration
Koldamova, R., Fitz, N. F., & Lefterov, I. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.007 · Cited by 144 · see citing works
Martins, R. N., Villemagne, V., Sohrabi, H. R., Chatterjee, P., Shah, T. M., Verdile, G., Fraser, P., Taddei, K., Gupta, V. B., Rainey-Smith, S. R., et al. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-171145 · Cited by 129 · see citing works
Self-citationRasmussen, K. L. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.10.037 · Cited by 125 · see citing works
Lipid metabolism in Alzheimer’s disease
Liu, Q., & Zhang, J. (2014) · Neuroscience Bulletin · doi:10.1007/s12264-013-1410-3 · Cited by 101 · see citing works
Morales-Narváez, E., Montón, H., Fomicheva, A., & Merkoçi, A. (2012) · Analytical Chemistry · doi:10.1021/ac301369e · Cited by 79 · see citing works
Han, S.-H., Park, J.-C., & Mook-Jung, I. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.12.004 · Cited by 67 · see citing works
Serum Levels of ApoA1 and ApoA2 Are Associated with Cognitive Status in Older Men
Ma, C., Li, J., Bao, Z., Ruan, Q., & Yu, Z. (2015) · BioMed Research International · doi:10.1155/2015/481621 · Cited by 46 · see citing works
Aslam, M. M., Fan, K.-H., Lawrence, E., Bedison, M. A., Snitz, B. E., DeKosky, S. T., Lopez, O. L., Feingold, E., & Kamboh, M. I. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02170-4 · Cited by 39 · see citing works
Hurtado, M. O., Kohler, I., & de Lange, E. C. M. (2018) · Bioanalysis · doi:10.4155/bio-2018-0135 · Cited by 34 · see citing works
Han, S.-H., Kim, J. S., Lee, Y., Choi, H., Kim, J.-W., Na, D. L., Yang, E. G., Yu, M.-H., Hwang, D., Lee, C., et al. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.028639 · Cited by 29 · see citing works
- Authors
- Gupta, V. B., Laws, S. M., Villemagne, V. L., Ames, D., Bush, A. I., Ellis, K. A., Lui, J. K., Masters, C., Rowe, C. C., Szoeke, C., Taddei, K., & Martins, R. N.
- Affiliations
- Edith Cowan University (AU)
- ORCID
- Venue
- Neurology
- Published
- 2011-03-22
- Volume
- 76
- Issue
- 12
- Pages
- 1091-1098
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W1994994999
- Cited by
- 149
- References
- 4
- Citations by year
- 2025: 1 · 2024: 6 · 2023: 6 · 2022: 13 · 2021: 9 · 2020: 10 · 2019: 8 · 2018: 7 · 2017: 7 · 2016: 10 · 2015: 18 · 2014: 20 · 2013: 17 · 2012: 14
- FWCI
- 11.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- Edith Cowan University Research Online (Edith Cowan University) (submittedVersion)
- Figshare (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- apolipoprotein E, Alzheimer's disease, APOE ε4, APOE3, biomarkers, Pittsburgh compound B PET, early Alzheimer's disease
- MeSH terms
- Aged, Aging, Alzheimer Disease, Aniline Compounds, Apolipoproteins E, Brain, Carbon Radioisotopes, Cognition Disorders, Cross-Sectional Studies, Heterozygote, Homozygote, Humans, Risk Factors, Thiazoles, Biomarkers, Amyloid beta-Peptides, Positron-Emission Tomography, Apolipoprotein E4
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
