Objective The origins of Alzheimer’s disease (AD) remain elusive. The long pre-clinical phase of AD is universally recognized, but it is not known when predisposition for AD develops nor when the first signs and symptoms become discernable. In this regard, an essential role is played by the ‘reserve’ capacity of the brain, which is built up in early life and acts as buffer against adverse risk factors later in life. However, life-time trajectories of build up and loss of reserve and its determinants remain poorly understood.In ORACLE, I aim to unravel the origins of AD by studying reserve across the entire life-span: from in utero to end of life. The underlying hypothesis is that etiologic factors exert their effect on the risk of AD during the entire life-span, through build-up and loss of reserve. Such life-course approach to study reserve is worldwide unique and constitutes truly ground-breaking research aimed at unraveling the earliest origins of AD. Key objectives are:1) To study trajectories of reserve across the entire lifespan.2) To study factors that shape reserve in early life.3) To study factors that determine onset and early loss of reserve.I will compile a life-course cohort that consists of three population-based samples totalling 40,829 persons that together cover the entire life-span: children in Generation R Study (in utero – 18 yrs); parents in Generation R Study (18–45 yrs); and the Rotterdam Study (45 yrs – death). Reserve will be quantified structurally using imaging techniques that measure volumetry, perfusion and connectivity as well as functionally by measuring cognitive and non-cognitive brain functions. I will study genetic and non-genetic risk factors of AD and their effects on reserve.Results from ORACLE will provide ground-breaking new insights into the earliest origins of AD. In turn, these insights are of major importance to enable the early identification of persons at highest risk of AD and develop targeted prevention for these persons. Fields of science medical and health sciencesbasic medicineneurologydementiaalzheimer Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-StG-2015 - ERC Starting Grant Call for proposal ERC-2015-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Coordinator ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM Net EU contribution € 1 495 715,00 Address Dr molewaterplein 40 3015 GD Rotterdam Netherlands See on map Region West-Nederland Zuid-Holland Groot-Rijnmond Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 495 715,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM Netherlands Net EU contribution € 1 495 715,00 Address Dr molewaterplein 40 3015 GD Rotterdam See on map Region West-Nederland Zuid-Holland Groot-Rijnmond Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 495 715,00