Next-generation imaging biomarkers of cortical microstructure for measuring presymptomatic cortical degeneration in Alzheimer's disease and associations with molecular pathology

Alzheimer's disease (AD) brain changes begin decades before symptoms. Initially, abnormal proteins are deposited, but it is the later loss of brain cells that most closely predicts symptomatic decline. Effective treatments have been elusive; targeting treatments earlier, before symptoms, may increase success. To do this we need sensitive methods for identifying at risk individuals and tracking progression. I will use advanced forms of MRI and PET brain scanning in people who have AD protein deposition but are asymptomatic, and will compare these newer techniques with established methods. I will also assess how early brain cell damage on MRI relates to new blood tests and sensitive memory tests for AD. I aim to: - Facilitate a step change in understanding of the timing and pattern of early brain cell damage in AD. - Determine the best approach to measuring microscopic brain changes. - Examine how brain cell breakdown is related to/mediated by toxic proteins.