期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
卷 1821, 期 2, 页码 295-302出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2011.11.005
关键词
Alzheimer's disease; Amyloid-beta peptide (A beta); Apolipoprotein E (apoE); apoE/A beta; Interaction; Lipoprotein
资金
- Alzheimer's Association [ZEN-08-899000]
- NIH/NIA [PO1AG021184]
- NIH [NS520138]
- American Health Assistance Foundation [ADR97006]
The association between apolipoprotein E (apoE) and amyloid-beta peptide (A beta) may significantly impact the function of both proteins, thus affecting the etiology of Alzheimer's disease (AD). However, apoE/A beta 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/A beta interactions in solution, specifically apoE and both endogenous and exogenous A beta from plasma, CSF and astrocyte conditioned media. By SEC analysis, A beta association with plasma and CNS lipoproteins is apoE-dependent. While endogenous A beta elutes to specific human plasma lipoproteins distinct from those containing apoE, it is the apoE-containing lipoproteins that absorb excess amounts of exogenous A beta 40. In human CSF, apoE, endogenous A beta and phospholipid elute in an almost identical profile, as do apoE, exogenous A beta and phospholipid from astrocyte conditioned media. Combining SEC fractionation with subsequent analysis for SDS-stable apoE/A beta. complex reveals that apoE-containing astrocyte lipoproteins exhibit the most robust interactions with A beta. Thus, standardization of the methods for detecting apoE/A beta 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 A beta homeostasis could potentially contribute to identifying a plasma biomarker currently over-looked because it has multiple components. (C) 2011 Elsevier B.V. All rights reserved.
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