AD is a devastating and incurable brain disorder causing the majority of dementia cases. AD is defined by common biological criteria and develops on a biological continuum where the disease course includes preclinical periods and starts long before dementia appears. Genetic risks and disease pathways differ between AD subgroups and precision-medicine (PM) approaches are required to develop successful interventions. The PMI-AD consortium will exploit our world-leading technologies and competences to stratify early-stage AD patients using novel mechanistic pathway-to-therapeutic algorithm to develop cost-effective, pathway-adapted diagnostics and early interventions to delay disease onset. We hypothesize that PM can be delivered based on optimized diagnostic tools utilizing innovative pathways and prediction modelling. PMI-AD will focus on Innate Immune (Ii)- and Synapse (S)-related genetics that are tightly coupled to AD risk and are frequently manifested as distinct phenotypes early in the disease. We will employ integrated clinical scores, Ii and S polygenic scores, fluid (blood, cerebrospinal) and MRI biomarkers in advanced statistical modelling using machine learning and deep-learning techniques for Ii and S pathway- and stage -stratification. Furthermore, we will test candidate substances in established experimental models (incl. patient-derived neuron-microglia cultures), to stratify patient groups and perform early therapeutic interventions. Early-stage and pre-clinical trials require use of focused medical nutrition and repurposed drugs with established safety profiles. We will perform cost assessments of health and care-impacts, and trans-European implementation. PMI-AD partners are world-leaders in genetics, biomarker development, machine learning, clinical trials and health economy. PMI-AD will cooperate closely with user-representatives and patient advocate groups to ensure maximal AD prevention effects at a European level.
Project leader: Tormod Fladby
Institution: Institutt for klinisk medisin