Exley, Christopher, House, Emily, Collingwood, Joanna F., Davidson, Mark R., Cannon, Danielle and Donald, A. M. (2010) Spherulites of Aβ42 in vitro and in Alzheimer's disease. Journal of Alzheimer's Disease, Vol.20 (No.4). pp. 1159-1165. doi:10.3233/JAD-2010-091630 ISSN 1387-2877.

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Abstract

Several amyloidogenic proteins including insulin, b-lactoglobulin and albumin, form spherulites in vitro under non-physiological conditions. These micrometer-sized, roughly spherical structures are composed of ordered arrays of amyloid fibrils in radial arrangements which, characteristically, show a typical Maltese cross pattern of light extinction under the polarizing microscope. The physiological significance of amyloid spherulites is unknown though in Alzheimer's disease senile plaques composed primarily of b sheets of Ab42 have, very occasionally, been shown to give a Maltese cross pattern of light extinction under crossed polarisers. Herein we describe the first observation of the formation in vitro of spherulites of Ab42. They were formed under near-physiological conditions in which the b sheet conformation of preformed aggregates of Ab42 had been abolished following the addition of an excess of copper. Incubation of these preparations at 37°C for up to 9 months resulted in the formation of globular structures, 5 - 20 mm in diameter, which exhibited a Maltese cross pattern of light extinction typical of spherulites. Near-identical spherulitic structures were also observed in abundance in 30 mm thick sections of Alzheimer's disease brain tissue. Synchrotron x-ray fluorescence showed that the location of these spherulites in AD tissue coincided with locally elevated concentrations of tissue copper. The formation in vitro of spherulites of Ab42 which morphologically appeared analogous to spherulitic structures observed in vivo strongly supports the hypothesis that spherulites and senile plaques in AD tissue are one and the same structures and that their ultimate formation may involve copper.

Item Type:	Journal Article
Alternative Title:	Spherulites of Amyloid-beta 42 in vitro and in Alzheimer's disease
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry R Medicine > RC Internal medicine
Divisions:	Faculty of Science, Engineering and Medicine > Engineering > Engineering
Library of Congress Subject Headings (LCSH):	Amyloid -- Research, Polarizing microscopes, Amyloid beta-protein -- Research, Alzheimer's disease -- Research, Copper -- Physiological effect, Copper -- Bioaccumulation
Journal or Publication Title:	Journal of Alzheimer's Disease
Publisher:	IOS Press
ISSN:	1387-2877
Official Date:	2010
Dates:	Date Event 2010 Published
Volume:	Vol.20
Number:	No.4
Number of Pages:	7
Page Range:	pp. 1159-1165
DOI:	10.3233/JAD-2010-091630
Status:	Peer Reviewed
Access rights to Published version:	Restricted or Subscription Access
Funder:	Engineering and Physical Sciences Research Council (EPSRC), National Institutes of Health (U.S.) (NIH)
Grant number:	EP/D066654/1 (EPSRC), R21NS060304 (NIH)

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