The project was conducted by researchers at the Fondation Recherche Alzheimer (FRA) reporting to Dr. Olivier de Ladoucette, Professor Dubois and Professor Hampel, respectively President, Scientific Director and Principal Investigator of FRA.
Duration of the Project: 2013 – 2022
The primary aim of this research program was to identify a precise set of reliable biomarkers (panels) reflecting the underlying pathophysiological pathways from molecular to functional connectivity mechanisms. Such panels provide a systematic and personalized classification of individuals into distinctive biological-functional stages of Alzheimer’s disease (AD), along the continuum. The scientific quality and originality of this program may significantly impact the research & development programs aiming to develop disease-modifying therapies for different stages of AD, throughout an innovative biomarker-guided process.
The project had the following objectives:
To evaluate whether alterations in specific functional networks, as measured by magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI), can be uniquely associated with specific pathophysiological molecular markers.
To understand the association between MEG and fMRI functional connectivity at rest according to the individual’s apolipoprotein E (APOE) genotype / genomic data (neuroimaging genetics).
Participants will be asked to perform a memory task during both fMRI acquisition and MEG registration and will be evaluated longitudinally, over at least 3 years. This task-related approach will allow researchers to investigate the brain areas impaired in AD-related conditions and to characterize the functional evolution of these areas in asymptomatic individuals at-risk for AD, according to their pathophysiological molecular marker profiles.
To untangle the link between molecular / cellular pathways underlying AD pathophysiology (i.e., pathophysiological molecular markers) and brain system connectivity. In particular, to perform a hypothesis-free exploration of how biomarkers charting distinct pathophysiological mechanisms may predict connectivity alterations over time. This could provide crucial insights into the development of potential biological therapeutic targets.
