DIVE into AD · Study of tau strains to understand the phenotypic diversity of Alzheimer’s disease: A step toward personalized therapies
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-08-01 → 2023-01-04
- EU contribution
- €190,208
- Participants
- 2
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Study of tau strains to understand the phenotypic diversity of Alzheimer’s disease: A step toward personalized therapies
Alzheimer’s disease (AD) is the most prevalent form of dementia and the most frequently occurring neurodegenerative disorder. While the life expectancy is continuously increasing in most countries, the number of AD cases is expected to increase massively in the near future. Understanding the underlying mechanisms of disease must be a priority in order to design effective therapies that are able to slow down or cure this debilitating disorder. AD is a heterogeneous disease that is responsible for a diversity of clinical presentations that include a wide spectrum of rate of cognitive decline or rare focal variants of the disease.The symptoms of AD are closely related to the accumulation in the brain of a protein named tau, that is able to propagate from one brain region to another. Abnormal tau protein can enter recipient neurons and recruit the normal tau inside neuron to build toxic aggregates. This process is called seeding. Differences in tau seeding at the individual level might be responsible for the heterogeneity of clinical presentation. We believe that the development of sensitive tools to characterize and measure tau seeding activity in biological samples will help not only to understand AD physiopathology but also to design more specific therapies that will benefit the society.
Data: CORDIS, © European Union
Project objective
Dementia represents a major challenge for our ageing societies. The number of citizens suffering from dementia in the EU is expected to reach 19 millions by 2050. Alzheimer’s disease (AD) is responsible for the vast majority of dementia cases. However there is still not a single available treatment that modifies the course of disease. Therefore, the development of innovative approaches to better understand the pathophysiology and ultimately treat patients must be a priority. This project aims to understand the determinants of the diversity of AD clinical phenotypes through the deep analysis of pathological variants of the tau protein. As the accumulation of Aβ peptide has long been considered a causative event in AD, most therapeutic approaches have targeted Aβ metabolism, but unsuccessfully. Modern biomarkers, have confirmed that the brain deposition of tau pathology, the other hallmark of AD, correlates much better with human cognition and neurodegeneration. Recently, it was shown that tau behaves like a prion and can spread from one neuron to another. Moreover, tau strains or conformers seem to template native tau and propagate the pathological conformation with high fidelity. Discrete tau strains generate distinct aggregates morphology or patterns of neuronal vulnerability. I postulate that different strains of tau are responsible for the variability of AD and may determine the progression rate, gender differences or clinical expression. Therefore, my objective is to develop the technologies to identify tau strains signatures in distinct AD phenotypes. In particular, I plan to develop and optimize biosensor cell lines that sensitively detect tau strains from human brain samples and cerebrospinal fluid, and characterize respective repertoire of tau strains. Understanding AD heterogeneity would potentially increase our ability to take care of every individual patient. In addition, this work could lead to the development of biomarkers and novel targeted therapies.
Original text from CORDIS.
Participants
- UNIVERSITE DE GENEVE · GeneveCoordinatorSwitzerland
- THE GENERAL HOSPITAL CORPORATION · BOSTON MAUnited States
Links
Data: CORDIS, © European Union