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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.

Coordinator

KAROLINSKA INSTITUTET
Net EU contribution
€ 247 059,00
Address
Nobels Vag 5
17177 Stockholm
Sweden

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00

Partners (1)

Partner

Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement.

THE ROCKEFELLER UNIVERSITY NOT FOR PROFIT CORPORATION
United States
Net EU contribution
€ 0,00
Address
York Avenue 1230
10065 New York

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Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 160 130,40