Project description
Understanding tau spread to tackle Alzheimer’s
Alzheimer’s disease (AD) poses significant societal and economic challenges, with over 99 % of clinical trials failing. One major issue is the inadequate stratification of patients due to the disease’s heterogeneity. Tau protein aggregates play a crucial role in AD, leading to neurodegeneration and dementia. Supported by the Marie Skłodowska-Curie Actions (MSCA) programme, the networkAD project will develop a novel, patient-specific network model to study tau spread. This model integrates global connectivity and regional brain vulnerability, using gene expression profiles. By providing mechanistic insights into tau propagation, the project aims to enhance patient selection in clinical trials. The resulting open-source software will facilitate replication and further research, aiming to improve treatment strategies.
Objective
Alzheimer’s disease (AD) has far-reaching societal and economic consequences, emphasizing the urgent need for effective treatment solutions. However, to date, over 99% of AD clinical trials have failed. Inadequate patient stratification is a key contributing factor due to the enormous clinical and pathological heterogeneity in AD. AD is characterized by the aggregation of pathogenic proteins, with tau aggregates being a key player. Tau-related pathological processes lead to synaptic dysfunction, neurodegeneration, and eventually dementia. It is thus of paramount importance to decipher the mechanisms of tau deposition and spread. Emerging evidence suggests that tau tangles accumulate along specific macroscale brain networks, lending support to the hypothesis of tau spreading through communicating neurons. Network-based spreading models have provided insights along this line. I aim to contribute to a leap in network-based modelling of tau spread, by developing a novel patient-specific network model, coupled with a diffusion framework to study tau spread. The model will be individualised, in contrast to previously used group-averaged designs, and will be hybrid, in two respects. First, the model will integrate global functional and structural connectivity. Second, it will integrate data on regional vulnerability of brain tissue for generating tau based on gene expression profiles from an atlas. Results will provide mechanistic insights into spread of tau. The model and its subtypes will then be used to define an optimal sample stratification scheme, to enhance patient selection in clinical trial designs. Importantly, designs and analysis methods developed as part of this action will be released as a unified open-source software package to allow replication, expansion, and increased impact. Altogether, this proposal will provide novel scientific outcomes and will provide me with critical training in scientific and transferable skills that will largely advance my career.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- natural sciences computer and information sciences software
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine neurology neurodegenerative diseases dementia
- medical and health sciences basic medicine pathology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Topic(s)
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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
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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22100 Lund
Sweden
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