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

Authors: LaDu, MJ  Munson, GW  Jungbauer, L  Getz, GS  Reardon, CA  Tai, LM  Yu, C 
Citation: LaDu MJ, etal., Biochim Biophys Acta. 2012 Feb;1821(2):295-302. Epub 2011 Nov 23.
Pubmed: (View Article at PubMed) PMID:22138302
DOI: Full-text: DOI:10.1016/j.bbalip.2011.11.005

The association between apolipoprotein E (apoE) and amyloid-beta peptide (Abeta) may significantly impact the function of both proteins, thus affecting the etiology of Alzheimer's disease (AD). However, apoE/Abeta 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/Abeta interactions in solution, specifically apoE and both endogenous and exogenous Abeta from plasma, CSF and astrocyte conditioned media. By SEC analysis, Abeta association with plasma and CNS lipoproteins is apoE-dependent. While endogenous Abeta elutes to specific human plasma lipoproteins distinct from those containing apoE, it is the apoE-containing lipoproteins that absorb excess amounts of exogenous Abeta40. In human CSF, apoE, endogenous Abeta and phospholipid elute in an almost identical profile, as do apoE, exogenous Abeta and phospholipid from astrocyte conditioned media. Combining SEC fractionation with subsequent analysis for SDS-stable apoE/Abeta complex reveals that apoE-containing astrocyte lipoproteins exhibit the most robust interactions with Abeta. Thus, standardization of the methods for detecting apoE/Abeta 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 Abeta homeostasis could potentially contribute to identifying a plasma biomarker currently over-looked because it has multiple components.

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RGD Object Information
RGD ID: 6903908
Created: 2012-10-08
Species: All species
Last Modified: 2012-10-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.