Abstract

The risk of developing AD is conferred through numerous genetic and environmental factors. How these risks influence brain structure prior to the onset of AD pathology is not yet known. We hypothesise that there may be specific anatomic endophenotypes that predispose to AD years before the first signs of amyloid accumulation occur. Using clinical, genetic and brain MRI data from Fundacio ACE Healthy Brain Initiative (FACEHBI), a longitudinal cohort of individuals with Subjective Cognitive Decline aged > 50 years, we identified a spatially-specific, fine-grained pattern of cortical thickness in frontal lobe regions among amyloid-negative individuals at baseline that holds a significant relationship with the rate of amyloid accumulation during the next five years. This pattern may represent a structural fingerprint of increased susceptibility to the initiation of the AD cascade.