Plasma apolipoprotein E and Alzheimer disease risk
The AIBL study of aging
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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 significance of these findings will be determined in the AIBL longitudinal study of aging.
Footnotes
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Study funding: Core funding for the study was provided by CSIRO, which was supplemented by in-kind contributions from the study partners (see http://www.aibl.csiro.au/). Richard Head of CSIRO initiated and facilitated the AIBL collaboration. The study also received support from the National Health and Medical Research Council (NHMRC) via the Dementia Collaborative Research Centres program (DCRC2). Pfizer International has contributed financial support to assist with analysis of blood samples and to further the AIBL research program. The McCusker Foundation has contributed financial and in-kind support to AIBL. Both Veer Bala Gupta and Simon Laws are research fellows at Edith Cowan University. Dr Gupta's salary is fully provided by Alzhyme Pty Ltd. Cassandra Szoeke is partially supported by a research fellowship funded by Alzheimer's Australia. Alzheimer's Australia (Victoria and Western Australia) assisted with promotion of the study and the screening of telephone calls from volunteers.
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- AD
- Alzheimer disease
- AIBL
- Australian Imaging, Biomarkers and Lifestyle study
- ANOVA
- analysis of variance
- HSD
- honestly significant differences
- MC
- memory complainers
- MCI
- mild cognitive impairment
- NMC
- nonmemory complainers
- PiB
- Pittsburgh compound B
- SUV
- standardized uptake value
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Supplemental data at www.neurology.org
- Received July 1, 2010.
- Accepted December 13, 2010.
- Copyright © 2011 by AAN Enterprises, Inc.
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