Project description
Going back to the drug design board for Alzheimer’s disease
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder caused by the accumulation of amyloid beta and tau protein aggregates in brain cells. Currently, there are no effective drugs available, suggesting that we need to revisit drug design for AD. The EU-funded TAU-NOW project is working under the hypothesis that new drugs should target tau spread and/or boost resilience to tau-related pathology. In this context, researchers are investigating the mechanism by which tau aggregates spread in the brain. Through a multi-disciplinary approach, they hope to identify molecular determinants in this process as well as factors that render individuals resilient to tau pathology.
Objective
Alzheimer’s disease (AD) poses a major challenge, as 40 million people worldwide are diagnosed with AD and there is currently no cure. AD is characterized by Aβ plaques and tau neurofibrillary tangles. Recently, several phase III clinical trials targeting the Aβ pathway have failed to reach their primary endpoints. This stresses the need for diversification of the drug portfolio. Tau pathology is a promising drug target due to its strong associations with synaptic density, atrophy and cognition. I envision two treatment options to be potentially effective in halting or slowing AD: 1) preventing the spreading of pathological tau, and 2) boosting resilience against tau pathology. Both processes are currently insufficiently understood, especially in living humans. Since a few years, AD-specific tau pathology can be measured in vivo using PET. TAU-NOW uniquely utilizes longitudinal tau PET in conjunction with functional and structural MRI, biofluid and cognitive data, to investigate mechanisms of tau spread and resilience in humans. In WP1, I will test the hypothesis that tau predominantly spreads through functionally connected regions, by relating tau PET changes over time to the functional architecture of the brain. Next, molecular (CSF) and genetic (GWAS) drivers of tau spread will be identified. On top of that, I will assess whether functional disconnection in subjects who underwent epileptic surgery (i.e. unilateral medial temporal lobe resection or corpus callosotomy) leads to an asymmetric tau PET pattern decades later. In WP2, I will investigate the functional (fMRI), molecular and genetic modifiers that render individuals resilient to tau pathology. In WP3, I will examine the consequences of tau spreading and resilience for important clinical trial outcomes like cognitive and volumetric changes over time. Altogether, TAU-NOW will enhance our understanding of tau spreading and resilience and may ultimately identify novel leads for drug discovery against AD.
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.
- medical and health sciences basic medicine neurology dementia alzheimer
- medical and health sciences clinical medicine surgery
- 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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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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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.
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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.
ERC-STG - Starting Grant
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Call for proposal
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(opens in new window) ERC-2020-STG
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22100 Lund
Sweden
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