Alzheimer Disease: Wilkinson H

Wilkinson H, Janicki MP, Anonymous00305. · Centre for Social Research on Dementia, Department of Applied Social Science, Faculty of Human Sciences, University of Stirling, UK. · J Intellect Disabil Res. · Pubmed #11896814 No free full text.

Abstract: A panel of experts attending a 3-day meeting held in Edinburgh, UK, in February 2001 was charged with producing a set of principles outlining the rights and needs of people with intellectual disability (ID)and dementia, and defining service practices which would enhance the supports available to them. The Edinburgh Principles, seven statements identifying a foundation for the design and support of services to people with ID affected by dementia, and their carers, were the outcome of this meeting. The accompanying guidelines and recommendations document provides an elaboration of the key points associated with the Principles and is structured toward a four-point approach: (1) adopting a workable philosophy of care; (2) adapting practices at the point of service delivery; (3) working out the coordination of diverse systems; and (4) promoting relevant research. It is expected that the Principles will be adopted by service organizations world-wide, and that the accompanying document will provide a useful and detailed baseline from which further discussions, research efforts and practice development can progress.

Martins IC, Kuperstein I, Wilkinson H, Maes E, Vanbrabant M, Jonckheere W, Van Gelder P, Hartmann D, D'Hooge R, De Strooper B, Schymkowitz J, Rousseau F. · Switch Laboratory, Flanders Institute for Biotechnology (VIB) and Vrije Universiteit Brussel, Brussel, Belgium. · EMBO J. · Pubmed #18059472 links to  free full text

Abstract: Although soluble oligomeric and protofibrillar assemblies of Abeta-amyloid peptide cause synaptotoxicity and potentially contribute to Alzheimer's disease (AD), the role of mature Abeta-fibrils in the amyloid plaques remains controversial. A widely held view in the field suggests that the fibrillization reaction proceeds 'forward' in a near-irreversible manner from the monomeric Abeta peptide through toxic protofibrillar intermediates, which subsequently mature into biologically inert amyloid fibrils that are found in plaques. Here, we show that natural lipids destabilize and rapidly resolubilize mature Abeta amyloid fibers. Interestingly, the equilibrium is not reversed toward monomeric Abeta but rather toward soluble amyloid protofibrils. We characterized these 'backward' Abeta protofibrils generated from mature Abeta fibers and compared them with previously identified 'forward' Abeta protofibrils obtained from the aggregation of fresh Abeta monomers. We find that backward protofibrils are biochemically and biophysically very similar to forward protofibrils: they consist of a wide range of molecular masses, are toxic to primary neurons and cause memory impairment and tau phosphorylation in mouse. In addition, they diffuse rapidly through the brain into areas relevant to AD. Our findings imply that amyloid plaques are potentially major sources of soluble toxic Abeta-aggregates that could readily be activated by exposure to biological lipids.