Identification of age-related Human Blood factors as a therapeutic target for Alzheimer's disease

Informations projet

HeBe

N° de convention de subvention: 948677

DOI

10.3030/948677

Projet clôturé

Date de signature de la CE 10 Novembre 2020

Date de début 1 Avril 2021

Date de fin 31 Mars 2026

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 1 498 915,00

Contribution de l’UE

€ 1 498 915,00

Coordonné par

FUNDACIO BARCELONABETA BRAIN RESEARCH CENTER
Spain

Periodic Reporting for period 3 - HeBe (Identification of age-related Human Blood factors as a therapeutic target for Alzheimer's disease)

Période du rapport: 2024-04-01 au 2025-09-30

Résumé du contexte et des objectifs généraux du projet

The HeBe project seeks to uncover potential therapeutic targets for Alzheimer's disease by investigating blood factors influencing brain ageing. Inspired by findings in mice, where some blood factors rejuvenated aging brains, the project takes a novel approach. We will investigate the blood from individuals that have a younger brain age and an older brain age than expected. By utilizing advanced proteomics and metabolomics, HeBe aims to identify blood factors associated with brain ageing and neurodegeneration. The project's central hypothesis posits that certain blood factors may influence the rate of neurodegeneration. If confirmed, this insight could pave the way for novel therapeutic avenues. The ultimate goal is to design a proof-of-concept clinical trial to explore lifestyle or pharmacological interventions that have an effect on these blood factors. HeBe marks a significant step in translating scientific discoveries into potential interventions for age-related brain diseases, such as Alzheimer’s disease.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The initial phase of HeBe focused on identifying individuals with extreme biological age phenotypes, determined through BrainAge computation from magnetic resonance imaging (MRI) data. This phase successfully delineated aging groups, including both "aged" and "rejuvenated" participants, setting the stage for the subsequent exploration of distinct blood factors associated with extreme age phenotypes.
The following step comprised comprehensive proteomic analyses on plasma samples from individuals exhibiting extreme biological age, categorizing them based on brain age relative to chronological age. Crucially, these analyses were sex-specific. Completion of these analyses on 340 samples marks a pivotal milestone for HeBe, providing a rich dataset currently under thorough analyses.
Furthermore, we conducted measurements of key Alzheimer's disease-related blood biomarkers in the ALFA cohort (https://www.barcelonabeta.org/en/alfa-study/about-the-alfa-study) identifying those blood biomarkers that indicate early amyloid- accumulation in the Alzheimer's continuum.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The most notable results we have achieved thus far involve the identification of blood biomarkers that change in the early stages of Alzheimer's disease, a significant contribution to the evolving landscape of preclinical Alzheimer's blood biomarkers. These biomarkers will play a crucial role in evaluating the potential associations between the rejuvenating and aging blood factors we pinpoint and Alzheimer's disease along with neurodegeneration. Currently, we are in the process of analysing the proteomic data to discern the proteins linked to brain aging.
As we approach the conclusion of the HeBe project, our anticipated outcomes involve assessing whether these newly identified blood factors exhibit associations with cognition, neurodegeneration, and Alzheimer's disease biomarkers. The HeBe project will ultimately determine whether these blood factors may be therapeutic targets for age-related diseases such as Alzheimer’s disease.