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Spherulites of Aβ42 in vitro and in Alzheimer's disease

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Exley, Christopher, House, Emily, Collingwood, Joanna F., Davidson, Mark R., Cannon, Danielle and Donald, A. M. (Athene Margaret), 1953-. (2010) Spherulites of Aβ42 in vitro and in Alzheimer's disease. Journal of Alzheimer's Disease, Vol.20 (No.4). pp. 1159-1165. ISSN 1387-2877

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Official URL: http://dx.doi.org/10.3233/JAD-2010-091630

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
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
Date:	2010
Volume:	Vol.20
Number:	No.4
Number of Pages:	7
Page Range:	pp. 1159-1165
Identification Number:	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)
References:	1.Krebs, M.R.H., MacPhee, C.E., Miller, A.F., Dunlop, I.E., Dobson, C.M., Donald, A.M. (2004) The formation of spherulites by amyloid fibrils of bovine insulin. Proc. Natl. Acad. Sci. USA 101, 14420-14424. 2.Bromley, E.H.C., Krebs, M.R.H., Donald, A.M. (2005) Aggregation across the length-scales in beta-lactoglobulin. Faraday Disc. 128, 13-27. 3.Juárez, J., Taboada, P. Goy-López, S., Cambón, A., Madec, M-B., Yeates, S.G., Mosquera, V. (2009) Additional supra-self-assembly of human serum albumin under amyloid-like-forming solution conditions. J. Phys. Chem. B 113, 12391-12399. 4.Ruth, L., Eisenberg, D. & Neufeld, E.F. (2000) a-L-Iduronidase forms semicrystalline spherulites with amyloid-like properties. Acta Cryst. D56, 524-528. 5.Yagi, N., Ohta, N., Lida, T., Inoue, K. (2006) A microbeam X-ray diffraction study of insulin spherulites. J. Mol. Biol. 362, 327-333. 6.Domike, K.R., Hardin, E., Armstead, D.N., Donald, A.M. (2009) Investigating the inner structure of irregular b-lactoglobulin spherulites. Eur. Phys. J. E. 29, 173-182. 7.Yagi, N., Ohta, N. & Matsuo, T. (2009) Structure of amyloid fibrils of hen egg white lysozyme studied by microbeam X-ray diffraction. Int. J. Biol. Macromol. 45, 86-90. 8.Domike, K.R. & Donald, A.M. (2009) Kinetics of spherulite formation and growth: Salt and protein concentration dependence on proteins b-lactoglobulin and insulin. Int. J. Biol. Macromol. 44, 301-310. 9.Jin, L-W., Klayborn, K.A., Kurimoto, M., Geday, M.A., Maezawa, I., Sohraby, F., Estrada, M., Kaminksy, W., Kahr, B. (2003) Imaging linear birefringence and dichroism in cerebral amyloid pathologies. Proc. Natl. Acad. Sci. USA 100, 15294-15298. 10.Snow, A.D., Sekiguchi, R., Nochlin, D., Fraser, P., Kimata, K., Mizutani, A., Arai, M., Schreier, W.A., Morgan, D.G. (1994) An important role of heparan sulphate proteoglycan (Perlecan) in a model system for the deposition and persistence of fibrillar Ab-amyloid in rat brain. Neuron 12, 219-234. 11. Hardy, J. & Allsop, D. (1991) Amyloid deposition as the central event in the aetiology of Alzheimers disease. Trends Pharmacol. Sci. 12, 383-388. 12.Mosselmans, J.F., Quinn, P.D., Dent, A.J., Cavill, S.A., Moreno, S.D., Peach, A., Leicester, P.J., Keylock, S.J., Gregory, S.R., Atkinson, K.D., Rosell, J.R. (2009) I18 - the microfocus spectroscopy beamline at the Diamond Light Source. J. Synchrotron Rad. 16, 818-824. 13.Collingwood, J.F., Mikhaylova A, Davidson, M.R., Batich, C., Streit, W.J., Eslin, T., Terry, J., Barrea, R., Underhill, R.S., Dobson, J. (2005) High resolution X-ray absorption spectroscopy studies of metal compounds in neurodegenerative brain tissue. J. Phys. Conf. Ser. 17, 54-60. 14. Solé V.A., Papillon, E., Cotte, M., Walter, P., Susini, J., (2007) A multiplatform code for the analysis of energy-dispersive X-ray fluorescence spectra. Spectrochim. Acta Part B 62, 63-68. 15.House, E., Mold, M., Collingwood, J.F., Baldwin, A., Goodwin, S., Exley, C. (2009) Copper abolishes the b-sheet secondary structure of preformed amyloid fibrils of Ab42. J. Alzh. Dis. 18, 811-817. 16.Bobin, S.A., Wisniewski, H.M., Kieras, F.J., Iqbal, K. (1981) Morphological and chemical characterization of a starch granule-like polyglucosan deposit isolated from human brain. Acta Neuropathol. (Berl.) 55, 47-52. 17.Kimura, T., Fujise, N., Ono, T., Shono, M., Yuzuriha, T., Katsuragi, S., Takamatsu, J., Miyakawa, T., Kitamura, T. (2002) Identification of an aging-related spherical inclusion in the human brain. Pathol. Int. 52, 636-642. 18.Srikanth, R., Mendoza, V.L., Bridgewater, J.D., Zhang, G., Vachet, R.W. (2009) Copper binding to b-2-microglobulin and its pre-amyloid oligomers. Biochemistry 48, 9871-9881. 19.Matthews, F.E., Brayne, C., Lowe, J., McKeith, I., Wharton, S.B., Ince, P.G. (2009) Epidemiological pathway of dementia: Attributable-risks at death in the Medical Research Council Cognitive Function and Ageing Study. PloS Med. 6, e1000180.
URI:	http://wrap.warwick.ac.uk/id/eprint/2482