Peripheral apoE isoform levels in cognitively normal APOE ε3/ε4 individuals are associated with regional gray matter volume and cerebral glucose metabolism
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art_3A10.1186_2Fs13195-016-023 ...
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Nielsen, Henrietta M.Chen, Kewei
Lee, Wendy
Chen, Yinghua
Bauer, Robert J.
Reiman, Eric
Caselli, Richard
Bu, Guojun
Affiliation
Univ Arizona, Dept PsychiatIssue Date
2017-01-30
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BIOMED CENTRAL LTDCitation
Peripheral apoE isoform levels in cognitively normal APOE ε3/ε4 individuals are associated with regional gray matter volume and cerebral glucose metabolism 2017, 9 (1) Alzheimer's Research & TherapyJournal
Alzheimer's Research & TherapyRights
Copyright © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Background: Carriers of the APOE epsilon 4 allele are at increased risk of developing Alzheimer's disease (AD), and have been shown to have reduced cerebral metabolic rate of glucose (CMRgl) in the same brain areas frequently affected in AD. These individuals also exhibit reduced plasma levels of apolipoprotein E (apoE) attributed to a specific decrease in the apoE4 isoform as determined by quantification of individual apoE isoforms in APOE epsilon 4 heterozygotes. Whether low plasma apoE levels are associated with structural and functional brain measurements and cognitive performance remains to be investigated. Methods: Using quantitative mass spectrometry we quantified the plasma levels of total apoE and the individual apoE3 and apoE4 isoforms in 128 cognitively normal APOE epsilon 3/epsilon 4 individuals included in the Arizona APOE cohort. All included individuals had undergone extensive neuropsychological testing and 25 had in addition undergone FDG-PET and MRI to determine CMRgl and regional gray matter volume (GMV). Results: Our results demonstrated higher apoE4 levels in females versus males and an age-dependent increase in the apoE3 isoform levels in females only. Importantly, a higher relative ratio of apoE4 over apoE3 was associated with GMV loss in the right posterior cingulate and with reduced CMRgl bilaterally in the anterior cingulate and in the right hippocampal area. Additional exploratory analysis revealed several negative associations between total plasma apoE, individual apoE isoform levels, GMV and CMRgl predominantly in the frontal, occipital and temporal areas. Finally, our results indicated only weak associations between apoE plasma levels and cognitive performance which further appear to be affected by sex. Conclusions: Our study proposes a sex-dependent and age-dependent variation in plasma apoE isoform levels and concludes that peripheral apoE levels are associated with GMV, CMRgl and possibly cognitive performance in cognitively healthy individuals with a genetic predisposition to AD.ISSN
1758-9193Version
Final published versionSponsors
Alzheimer's Association [2015-NIRG-339824]; Younkin Scholars Program; Swedish Governmental Agency for Innovation Systems/VINNOVA [2015-04905]; NIH grants [RF1AG051504, R01AG046205, R01AG035355, P01NS074969, P50AG016574]Additional Links
http://alzres.biomedcentral.com/articles/10.1186/s13195-016-0231-9ae974a485f413a2113503eed53cd6c53
10.1186/s13195-016-0231-9
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Except where otherwise noted, this item's license is described as Copyright © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).