Journal article

Amino-terminal domain stability mediates apolipoprotein E aggregation into neurotoxic fibrils

Danny M Hatters, Ning Zhong, Earl Rutenber, Karl H Weisgraber

Journal of Molecular Biology | ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD | Published : 2006


The three isoforms of apolipoprotein (apo) E are strongly associated with different risks for Alzheimer's disease: apoE4>apoE3>apoE2. Here, we show at physiological salt concentrations and pH that native tetramers of apoE form soluble aggregates in vitro that bind the amyloid dyes thioflavin T and Congo red. However, unlike classic amyloid fibrils, the aggregates adopt an irregular protofilament-like morphology and are seemingly highly alpha-helical. The aggregates formed at substantially different rates (apoE4>apoE3>apoE2) and were significantly more toxic to cultured neuronal cells than the tetramer. Since the three isoforms have large differences in conformational stability that can influ..

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University of Melbourne Researchers