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Understanding selective neuronal vulnerability in Alzheimer’s disease

Objective

The aim of this action is to understand the mechanisms behind the susceptibility of enthorinal cortex II (ECII) neurons to neurofibrillary tangle (NFT) formation in Alzheimer´s disease. To do so we will modulate the expression of the genes that according to NetWAS (Network-wide Association Study) are more directly involved in NFT formation in ECII neurons.

Understanding why the pathological lesions that lead to neurodegeneration appear earlier in some specific neurons of the human brain is one of the major challenges in the neuroscience field.

Prof. Greengard´s lab has generated a transgenic mouse that allows the immunoprecipitation of ribosome-bound mRNAs specifically from ECII neurons (ECII-bacTRAP mice). We will perform AAV stereotaxic injections in the enthorinal cortex of these mice followed by RNA-seq to determine how the modulation of our target genes affects ECII neurons expression profile. We will also explore whether our intervention can influence ECII neurons susceptibility to NFT in P301S AD mice. The results obtained in mice will be validated by immunofluorescence and in situ hybridization studies in human samples from control and AD patients at different Braak stages.

Our results could add extremely relevant information on the mechanisms underlying AD pathogenesis and reveal these genes as new therapeutic targets for the disease.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF-GF - Global Fellowships

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2017

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Coordinator

KAROLINSKA INSTITUTET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 247 059,00
Address
NOBELS VAG 5
171 77 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 247 059,00

Partners (1)

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