Project description
Precision medicine in Alzheimer’s disease
Alzheimer’s disease (AD) is the most common form of dementia, and its pathophysiology is primarily defined by amyloid plaques. Patients, however, exhibit large differences in their underlying disease processes, which hampers treatment development. Recent evidence from cerebrospinal fluid (CSF) proteomics has identified five distinct AD subtypes with unique molecular processes and rates of cognitive decline, suggesting a need for personalised therapies. The ERC-funded DecipherAD project aims to characterise these subtypes by analysing large datasets of CSF proteomics over time and identifying genetic drivers. Researchers will also assess how subtypes respond to amyloid-targeting drugs and develop blood-based markers for easier diagnosis. Collectively, the work is expected to improve AD diagnosis and treatment.
Objective
Worldwide, 50 million people suffer from dementia, which is caused by Alzheimer’s disease (AD) in 70% of the cases. There is no treatment to stop, reverse or prevent AD. AD is pathologically defined by amyloid plaques and tau tangles in the brain, implying that it is a single disease entity. Still, patients vary greatly in rate of decline and underlying pathophysiology, which hampers the search for cures. I have discovered and replicated 5 AD subtypes in patients based on cerebrospinal fluid proteomics (CSF). Subtypes had distinct pathophysiology, including differences in amyloid metabolism and clearance, as well as in cognitive decline. This indicates that they would need tailored treatments.
The goal of this project is to understand AD subtype specific mechanisms, and how these are related to cognitive decline, taking CSF proteomics as a starting point. I will address the following scientific needs:
1. Understand which AD subtype molecular processes change over time, and how those changes relate to cognitive decline. This requires large datasets of individuals with repeated CSF proteomics. I have access to two large, deeply phenotyped cohorts with already collected repeated CSF samples over 5 years from 700 individuals, in which I will measure proteomics.
2. Study drivers of AD subtypes with genetics and in a subset of n=50 with tissue proteomics.
3. Develop markers in blood for subtype detection, which would remove barriers for clinical use.
4. Test if AD subtypes differently respond to amyloid modifying drugs, which is the strongest proof that AD subtypes need tailored therapy.
If successful, DecipherAD will provide proof of concept that AD subtypes have use as a theragnostic tool, show which genetic factors drive molecular subtypes, how molecular signatures change over time and how these changes relate to cognitive decline, with tools in blood to facilitate implementation in clinical practice. This will catalyse AD subtype tailored treatment development.
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.
This project's classification has been human-validated.
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.
This project's classification has been human-validated.
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.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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-ERC - HORIZON ERC Grants
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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) ERC-2024-COG
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1081 HV Amsterdam
Netherlands
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