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Are senile plaques, the characteristic pathological markers of Alzheimer’s disease, really spherulites?

Date:
June 15, 2010
Source:
Keele University
Summary:
Scientists believe they may have identified the true in vivo structure of the senile plaques that are characteristically found in the brains of people with Alzheimer's disease.

A team of scientists from Britain and the United States believe they may have identified the true in vivo structure of the senile plaques that are characteristically found in the brains of people with Alzheimer's disease.

The group, from the universities of Keele, Warwick, Cambridge and Florida, have shown for the first time that the amyloid-forming peptide, which is at the centre of the Amyloid Cascade Hypothesis of Alzheimer's disease (known as Aβ42), not only forms spherulites in test tube preparations but that similar, if not identical structures, are also present in the Alzheimer's disease brain.

Now Dr Chris Exley, Reader in Bioinorganic Chemistry at The Birchall Centre, Keele University, Staffordshire, who led the collaborative effort, says their findings are a significant breakthrough in understanding the true nature and form of senile plaques in living brain tissue and consequently how plaques are formed and their potential relevance as diagnostic tools for Alzheimer's disease.

Amyloid-forming proteins and peptides are known to adopt many different structural forms. Some of these forms, such as those for Aβ42 which, collectively, constitute the Amyloid Cascade Hypothesis of Alzheimer's disease, are implicated in the aetiology of disease, for example being neurotoxic under certain conditions.

The amyloid-forming proteins insulin and β-lactoglobulin, in addition to forming amyloid fibrils, have previously been shown to be organised into globular arrangements of such fibrils, which have been called spherulites. While the propensity for such proteins to form fibrillar material has been implicated in potential disease aetiologies, there has not hitherto been any physiological significance ascribed to their rearrangement into spherulites.

The spherulites of Aβ42 which the team have now observed in vitro were also globular in appearance, approximately 20-25 mm in diameter and were composed of radially arranged β sheets of the peptide. Many of the spherulites appeared to have a non-protein central core and all gave a classical Maltese cross pattern of light extinction when viewed under the polarising microscope.

The team then proceeded to observe apparently identical structures in Alzheimer's disease brain tissue. These AD spherulites were most often observed in thicker (30 as opposed to the usual 5 mm thickness) sections of AD brain tissue and this caused them to speculate that spherulites are actually what are presently being identified as senile plaques. The latter actually being 'sections' of spherulites as tissue is normally processed for AD histochemistry at 5 mm thickness.

If senile plaques are actually spherulites then this will have implications for their role in the aetiology of AD. The spherulites observed in vitro took many months to form and appeared to involve a metal-catalysed (possibly copper or aluminium) reorganisation of preformed β sheets of Aβ42. Thus, if true, then senile plaques and/or spherulites are not simply random deposits of peptide in a β sheet conformation but are specifically organised arrays of peptide within a stable globular structure.

The spherulites that formed in vitro, and were observed in AD, were of similar size to senile plaques and their radial arrangement of β sheets of Aβ42 is very similar to the appearance of senile plaque 'cores' when observed under the electron microscope. Further research will be needed to support the contention that senile plaques and spherulites are one and the same structure.

The research will be published in the July issue of the Journal of Alzheimer’s Disease and is a collaborative effort (Keele, Warwick, Cambridge, Florida) headed by Chris Exley at The Birchall Centre, Keele University.


Story Source:

The above story is based on materials provided by Keele University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Christopher Exley, Emily House, Joanna F. Collingwood, Mark R. Davidson, Danielle Cannon, Athene M. Donald. Spherulites of Amyloid-β42 In Vitro and in Alzheimer's Disease. Journal of Alzheimer's Disease, 2010; DOI: 10.3233/JAD-2010-091630

Cite This Page:

Keele University. "Are senile plaques, the characteristic pathological markers of Alzheimer’s disease, really spherulites?." ScienceDaily. ScienceDaily, 15 June 2010. <www.sciencedaily.com/releases/2010/06/100610104726.htm>.
Keele University. (2010, June 15). Are senile plaques, the characteristic pathological markers of Alzheimer’s disease, really spherulites?. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2010/06/100610104726.htm
Keele University. "Are senile plaques, the characteristic pathological markers of Alzheimer’s disease, really spherulites?." ScienceDaily. www.sciencedaily.com/releases/2010/06/100610104726.htm (accessed July 30, 2014).

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