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Preferential interactions between ApoE-containing lipoproteins and Aβ revealed by a detection method that combines size exclusion chromatography with non-reducing gel-shift

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posted on 27.06.2012, 00:00 authored by Mary Jo LaDu, Gregory W. Munson, Lisa Jungbauer, Godfrey S. Getz, Catherine A. Reardon, Leon M. Tai, Chunjiang Yu
The association between apolipoprotein E (apoE) and amyloid-β peptide (Aβ) may significantly impact the function of both proteins, thus affecting the etiology of Alzheimer's disease (AD). However, apoE/Aβ interactions remain fundamentally defined by the stringency of the detection method. Here we use size exclusion chromatography (SEC) as a non-stringent approach to the detection of apoE/Aβ interactions in solution, specifically apoE and both endogenous and exogenous Aβ from plasma, CSF and astrocyte conditioned media. By SEC analysis, Aβ association with plasma and CNS lipoproteins is apoE-dependent. While endogenous Aβ elutes to specific human plasma lipoproteins distinct from those containing apoE, it is the apoE-containing lipoproteins that absorb excess amounts of exogenous Aβ40. In human CSF, apoE, endogenous Aβ and phospholipid elute in an almost identical profile, as do apoE, exogenous Aβ and phospholipid from astrocyte conditioned media. Combining SEC fractionation with subsequent analysis for SDS-stable apoE/Aβ complex reveals that apoE-containing astrocyte lipoproteins exhibit the most robust interactions with Aβ. Thus, standardization of the methods for detecting apoE/Aβ complex is necessary to determine its functional significance in the neuropathology characteristic of AD. Importantly, a systematic understanding of the role of apoE-containing plasma and CNS lipoproteins in Aβ homeostasis could potentially contribute to identifying a plasma biomarker currently over-looked because it has multiple components.


This work was supported by grants from the Alzheimer's AssociationZEN-08-899000 (MJL), NIH/NIAPO1AG021184 (MJL), NIH NS520138 (GSG) and American Health Assistance Foundation ADR97006 (GSG).


Publisher Statement

NOTICE: this is the author’s version of a work that was accepted for publication in Biochimica et Biophysica Acta. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochimica et Biophysica Acta, Vol 1821, Issue 2, (February 2012) doi.org/10.1016/j.bbalip.2011.11.005







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