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.
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.
Authors: Jon B Toledo; Xiao Da; Michael W Weiner; David A Wolk; Sharon X Xie; Steven E Arnold; Christos Davatzikos; Leslie M Shaw; John Q Trojanowski Journal: Acta Neuropathol Date: 2014-01-03 Impact factor: 17.088
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Authors: Nicholas F Fitz; Andrea A Cronican; Muzamil Saleem; Abdul H Fauq; Robert Chapman; Iliya Lefterov; Radosveta Koldamova Journal: J Neurosci Date: 2012-09-19 Impact factor: 6.167
Authors: Holly D Soares; William Z Potter; Eve Pickering; Max Kuhn; Frederick W Immermann; David M Shera; Mats Ferm; Robert A Dean; Adam J Simon; Frank Swenson; Judith A Siuciak; June Kaplow; Madhav Thambisetty; Panayiotis Zagouras; Walter J Koroshetz; Hong I Wan; John Q Trojanowski; Leslie M Shaw Journal: Arch Neurol Date: 2012-10
Authors: James D Doecke; Simon M Laws; Noel G Faux; William Wilson; Samantha C Burnham; Chiou-Peng Lam; Alinda Mondal; Justin Bedo; Ashley I Bush; Belinda Brown; Karl De Ruyck; Kathryn A Ellis; Christopher Fowler; Veer B Gupta; Richard Head; S Lance Macaulay; Kelly Pertile; Christopher C Rowe; Alan Rembach; Mark Rodrigues; Rebecca Rumble; Cassandra Szoeke; Kevin Taddei; Tania Taddei; Brett Trounson; David Ames; Colin L Masters; Ralph N Martins Journal: Arch Neurol Date: 2012-10
Authors: Noll L Campbell; Fred Unverzagt; Michael A LaMantia; Babar A Khan; Malaz A Boustani Journal: Clin Geriatr Med Date: 2013-11 Impact factor: 3.076