CORDIS - EU research results
CORDIS

Study of tau strains to understand the phenotypic diversity of Alzheimer’s disease: A step toward personalized therapies

Project description

Role of tau strain diversity in the phenotypes of Alzheimer’s disease

Dementia is a global challenge in our ageing world. Alzheimer’s disease (AD) is responsible for most dementia cases, yet no treatment is available. The EU-funded DIVE into AD project is searching for the determinants of AD clinical phenotypes via the analysis of pathological variants of the tau protein. It has been confirmed that tau deposition in the brain correlates with the hallmarks of AD neurodegeneration. Tau protein behaves like a prion and can spread from one neuron to another, and discrete tau strains generate distinct aggregates morphology and patterns of neuronal vulnerability. Therefore, the project's objective is to develop the technologies to identify tau strain fingerprints in different AD phenotypes.

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.

Coordinator

UNIVERSITE DE GENEVE
Net EU contribution
€ 190 207,68
Address
RUE DU GENERAL DUFOUR 24
1211 Geneve
Switzerland

See on map

Region
Schweiz/Suisse/Svizzera Région lémanique Genève
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 190 207,68

Partners (1)