PMID: 8939715Nov 1, 1996Paper

An ApoE-Abeta inhibition complex in Abeta fibril extension

Chemistry & Biology
S J WoodR Wetzel

Abstract

Literature reports differ dramatically in showing that apolipoprotein E either facilitates or inhibits Abeta aggregate formation in vitro. Resolution of the nature of the ApoE-Abeta interaction is critical for progress towards understanding its possible role in the modulation of Alzheimer's disease. Here, we show that purified ApoE-Abeta co-aggregate is a poor seed of fibril formation. We also demonstrate ApoE inhibition of Abeta fibril growth in four independent aggregation assays, arguing that the poor fibril formation observed under these conditions is real and not an analytical artifact. We also directly show ApoE binding to immobilized Abeta fibrils by surface plasmon resonance. The results suggest a unifying model in which ApoE binds to Abeta fibril seeds and nascent nuclei to generate stable complexes that inhibit the rapid extension of mono-component Abeta fibrils but at the same time can foster continued slow growth of mixed ApoE-Abeta aggregates. In vivo co-aggregate formation may be important in many examples of pathological protein misassembly.

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Citations

May 23, 2012·Proceedings of the National Academy of Sciences of the United States of America·Carl Frieden, Kanchan Garai
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·T Kowalewski, D M Holtzman
Oct 18, 2015·Archives of Biochemistry and Biophysics·Laia Montoliu-Gaya, Sandra Villegas
Apr 15, 2004·Analytical Biochemistry·Michelle J CannonDavid G Myszka
Jul 6, 2002·Anais Da Academia Brasileira De Ciências·Fernanda G Defelice, Sergio T Ferreira
Feb 5, 2008·Biochemical and Biophysical Research Communications·Peng LeiYan-mei Li
Mar 1, 1997·Nature Biotechnology·H Döbeli
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Jun 13, 2019·Molecular Neurodegeneration·Ramsey NajmYadong Huang
May 10, 2002·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·William P EslerJohn E Maggio
Mar 17, 2011·Molecular BioSystems·Qian LiuYan-mei Li
Jul 23, 2018·Molecular Neurobiology·Md Sahab UddinGhulam Md Ashraf
Jan 2, 2014·Biotechnology, Biotechnological Equipment·Karen Pillay, Patrick Govender
Feb 19, 2019·Journal of Alzheimer's Disease : JAD·Alejandro R RodaSandra Villegas
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Aug 30, 2021·Molecular Neurodegeneration·M Mahafuzur Rahman, Christofer Lendel

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