Taking the long view: Identification of plasma protein biomarkers for dementia risk

Alzheimer's disease (the commonest dementia cause) is thought to be caused by two proteins/peptides in the brain, called amyloid and tau. Numerous drugs trials, targeting and sometimes reducing these biomarkers have failed to prevent disease or reduce deterioration. Studies looking for blood proteins have recruited people, aged over 65, followed-up for under 10 years. Therefore, biomarkers identified may be cause of or consequence of dementia.

Our collaborative team (experts in cohorts, causal inference, biomarkers, dementia, drug development) takes a different approach. We have blood stored from 1-25 years before dementia onset; from UK, US and Norwegian cohorts, in people followed to old age. We will analyse thousands of blood proteins from these midlife samples for new proteins associated with risk or protection from dementia, then check findings in independent cohorts. We will examine whether the associations represent cause-and-effect relationships.

Our results will identify new targets for preventing or delaying dementia.