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Functional consequence of apolipoprotein E/amyloid peptide interaction in Alzheimer’s disease amyloid proteopathy
Author(s) -
Cohen Jenny K,
Hawbecker Sharon K,
TamamizuKato Shiori,
Narayanaswami Vasanthy
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a502-a
Subject(s) - apolipoprotein e , cerebral amyloid angiopathy , lipoprotein , apolipoprotein b , amyloid (mycology) , amyloid precursor protein , pathogenesis , chemistry , gene isoform , p3 peptide , biochemistry of alzheimer's disease , presenilin , biochemistry , alzheimer's disease , peptide , lrp1 , microbiology and biotechnology , medicine , cholesterol , ldl receptor , biology , gene , disease , dementia , inorganic chemistry
Apolipoprotein (apo) E is an exchangeable apolipoprotein that plays an integral role in amyloid pathogenesis involved in Alzheimer’s disease (AD) and cerebral amyloid angiopathy. It is composed of an N‐terminal and a C‐terminal (CT) domain harboring lipoprotein receptor‐binding site and high affinity lipid binding sites, respectively. The ability to interact with lipoprotein surfaces is a key feature of apoE that allows it to mediate cellular clearance and uptake of lipoprotein particles. In addition, apoE also mediates protein misfolding or amyloid proteopathy involving deposition of amyloid peptide (Aβ) as fibrils in extra‐neuronal space or in the cerebral vasculature of AD bearers in an isoform‐specific manner. The objective of this study was to examine the role of Aβ association on the ability of recombinant human apoE to interact with lipid surfaces. Aβ was preincubated with apoE CT domain for varying lengths of time and at varying proportions of protein and Abeta, followed by lipid binding assay, Western blot and fluorescence analyses. Inter molecular fluorescence resonance energy transfer analysis indicated complex formation and tight interaction between apoE CT domain and Aβ. We note that the ability of apoE CT domain to interact with lipids was severely compromised following its interaction with Aβ. These results have serious implications not only in terms of amyloid build‐up, but also accumulation of cholesterol at extra cellular sites, which in turn leads to stroke if occurring in the cerebral microvasculature. Funded by the Alzheimer’s Association.