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Unveiling human astrocyte states, functions and their contribution to Alzheimer´s disease

Project description

Human astrocytes and their impact on Alzheimer’s disease

Alzheimer’s disease (AD) remains poorly understood and currently has no cure. Existing therapeutic targets are limited and insufficient, highlighting the urgent need to identify new mechanisms, pathways and treatment strategies. However, progress has been hindered by species-specific differences and the limitations of traditional rodent models. To address this challenge, the ERC-funded hASTROCURE project will use humanised chimeric mice to study human astrocytes (h-astrocytes) – key brain cells that remain largely unexplored in the context of AD. Through a multidisciplinary approach, the project aims to deepen our understanding of AD development and progression, and to clarify the role of h-astrocytes in these processes. The findings are expected to pave the way for novel therapeutic interventions.

Objective

The pathogenesis of Alzheimer´s disease (AD) is not fully understood and no cure is available so far. Current therapeutic targets are insufficient and there is an urgent need for finding new pathways and mechanisms and novel targets to treat this terrible disease. Due to critical species-specific differences and the limitations of rodent models of AD, humanized models are necessary to capture the complexity of the disease process. My lab has pioneered the use of humanized chimeric mice to study human astrocytes (h-astrocytes), integral components of the brain and understudied in AD. I propose here to investigate with a multidisciplinary approach their contribution to AD development and progression.
We have already showed the potential of chimeric mice to identify novel and unexpected contributions of h-astrocytes to AD pathology. hASTROCURE will take advantage of our unique model to drive breakthrough discoveries in our understanding of h-astrocytes and their role in AD. We will investigate in humanized chimeras what is the impact of the genetic make-up (risk vs protective variants in AD risk genes) on h-astrocytes molecular states and functions as disease evolves and how they contribute to pathological features and AD progression. The overarching aim is to dissect central pathways leading to h-astrocyte activation towards detrimental states and target those pathways, which can provide the necessary knowledge to enable the development of novel astrocyte-specific therapeutic strategies.
This pioneering project involves a set of innovative approaches as an essential platform for studying human genetics in h-astrocytes, in an AD relevant context. My experience and the work that my lab has developed these last years support the conceptual basis of the proposal and demonstrate its feasibility. hASTROCURE will go beyond the state-of-the-art providing groundbreaking information about h-astrocytes and their contribution to AD, and will help to define new strategies for AD.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-COG

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Host institution

ACHUCARRO BASQUE CENTER FOR NEUROSCIENCE FUNDAZIOA
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.

€ 1 999 875,00
Address
PARQUE CIENTIFICO DE LA UNIVERSIDAD DEL PAIS VASCO RRIKO UNIBERTSITATEA EDIFICIO SEDE PLANT A 3
48940 Leioa
Spain

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Region
Noreste País Vasco Gipuzkoa
Activity type
Research Organisations
Links
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.

€ 1 999 875,00

Beneficiaries (1)

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