ALZPROTAGEING

Age-modified forms of Amyloid-β as initiator of Alzheimer Disease pathogenesis and mediator of Aβ-tau interaction: a study in a Drosophila model and Aβ immunized human Alzheimer patients

Coordinatore	UNIVERSITY OF SOUTHAMPTON    more  Organization address address: Highfield city: SOUTHAMPTON postcode: SO17 1BJ contact info Titolo: Mrs. Nome: Yan Cognome: Qiao Email: send email Telefono: +44 2380593907
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	221˙606 €
EC contributo	221˙606 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2013-IEF
Funding Scheme	MC-IEF
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-03-01   -   2016-02-29

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITY OF SOUTHAMPTON  Organization address address: Highfield city: SOUTHAMPTON postcode: SO17 1BJ contact info Titolo: Mrs. Nome: Yan Cognome: Qiao Email: send email Telefono: +44 2380593907	UK (SOUTHAMPTON)	coordinator	221˙606.40

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 Obiettivo del progetto (Objective)

'Alzheimer Disease (AD) is the commonest form of dementia, with ageing as the main risk factor. There are currently over 6 million people with dementia in the European Union (EU). The increasingly ageing population makes AD an economic and social burden for our society, thus investigating the pathological mechanisms of AD and the characterization of the pharmacological targets are research priorities. Aggregation of amyloid-Beta (Aβ), upstream of tau phosphorylation, is considered a driving force in AD pathogenesis, and the major target of the clinical trials of immunotherapy. The first clinical trial at Southampton University (UoS) showed Aβ removal but also reduced phospho-tau, supporting a link between these proteins. Similar evidence emerged in bigenic tau/Aβ Drosophila, a neurodegeneration model. During ageing in humans, the molecules of AD pathogenesis undergo ageing processes resulting in amino acid modifications that influence protein folding, functionality and interactions. Specially, pyroglutamate-modified Aβ (pEAβ) seems to be a key participant in AD pathology. Accordingly, the identification of markers of protein ageing is important to comprehend AD pathogenesis with relevance in therapies. Indeed, Aβ immunotherapy did not improve the cognition in the treated patients, potentially due to the absence of clearance of aged-modified Aβ implicated in pathological pathways. I propose to exploit the bigenic tau/Aβ drosophila to determine if pEAβ increases with ageing, driving AD pathogenesis; and whether pEAβ is the major Aβ form mediating Aβ/tau interaction. Taking advantage of the unique cohort of human unimmunized and immunized AD brains at UoS, I will investigate if pEAβ formation and its interaction with tau have been modified by Aβ immunotherapy. The results will expand the Aβ characterization as a pharmacological target, and support the rational design of a second generation of “Aβ immunotherapies”. This project sustains the EU strategies to tackle AD.'