Project description
Structural and functional study of synaptic ApoE4 with unprecedented resolution
Tremendous advances have shed increasingly detailed light on the molecular basis of Alzheimer's disease. Tau pathology is of particular importance as it contributes to the damage and destruction of synapses that mediate memory loss. The ApoE4 isoform of brain apolipoprotein E (ApoE, a protein essential for lipid transport to neurons and thus healthy synaptic function) contributes to tau-mediated neurodegeneration and is the strongest genetic risk factor for Alzheimer's disease. ApoE is mainly produced by astrocytes. The ERC-funded SynApoE project aims to test the hypothesis that ApoE4 worsens tau-mediated synaptic degeneration y altering astrocyte-neuron interactions at the synapse. It will do so using cutting-edge techniques with unprecedented synaptic resolution.
Objective
Alzheimers disease (AD) is one of the biggest scientific and socio-economic challenges of the 21st century. Currently, there is no cure. Aggregates of amyloid- and tau protein, along with neuroinflammation/gliosis, are hallmarks of AD that lead to synaptic and neuronal loss as the basis for cognitive decline. The latter correlates closely with the brain distribution of tau aggregates, providing a strong incentive to investigate a link between tau accumulation and synaptic degeneration.
Brain apolipoprotein E (ApoE), mainly produced by astrocytes, is essential for lipid transport to neurons and synaptic functions. ApoE4 isoform is the strongest genetic risk factor for AD and contributes to tau-mediated neurodegeneration. Determining how ApoE4 controls tau-mediated synaptic degeneration is thus essential to understand AD and develop efficient treatments, yet this requires fine characterization of ApoE4 functions at tau-damaged synapses with a synaptic resolution.
SynApoE will test in 3 work packages the hypothesis that ApoE4 worsens tau-mediated synaptic degeneration by altering the astrocyte/neuron interactions at the synapse:
1: SYNAPTIC CHANGES. Identify directly at tau-damaged synapses the ApoE4-mediated structural and functional synaptic changes;
2: PROTEIN PLAYERS. Identify the protein players underlying these structural and functional synaptic changes;
3: MECHANISMS. Discover the mechanisms through which ApoE4 promotes tau-associated synaptic degeneration, based on the protein players identified in WP2.
SynApoE aims to decipher how ApoE4 drives tau-mediated synaptic degeneration, providing a deeper understanding of AD pathophysiology. SynApoE achieves unprecedented synaptic resolution by combining advanced proteomics, super resolution microscopy at synapses, electrophysiology and behavioral testing. This will help unravel the mechanisms leading to synaptic loss and subsequent cognitive decline, providing new targets for drug design to protect synapses.
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 biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences basic medicine neurology dementia alzheimer
- medical and health sciences basic medicine physiology pathophysiology
- natural sciences physical sciences optics microscopy
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
Topic(s)
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.
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
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.
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
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-STG
See all projects funded under this callHost institution
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.
75794 PARIS
France
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.