Project: Precision Medicine Interventions in Alzheimer’s Disease

Acronym PMI-AD (Reference Number: JPND2019-466-236)
Project Topic AD is a devastating and incurable brain disorder causing the majority of dementia cases. AD slowly destroys memory, thinking and cognitive skills leading to complete dependency on family or health care services and death. 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 (mechanisms and cellular responses) 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 (SP1) in advanced statistical modelling using machine learning and deep-learning techniques for Ii and S pathway- and stage -stratification (SP2.1). Furthermore, we will test candidate substances in established experimental models (incl. patient-derived neuron-microglia cultures) (SP 2.2), to stratify patient groups (SP2.3) and perform early therapeutic interventions (SP3). 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 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 partner

Number Name Role Country
1 University of Oslo Coordinator Norway
2 Göterborgs Universitet Partner Sweden
3 UMC Ljubljana Partner Slovenia
4 University of Copenhagen Partner Denmark
5 VU University Medical Center Partner Netherlands
6 Karolinska Institutet Partner Sweden
7 University of Medicine and Pharmacy Bucharest Partner Romania