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.
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.