Distinct spatiotemporal subtypes of amyloid deposition are associated with diverging disease profiles in cognitively normal and mild cognitive impairment individuals

We aimed to investigate the relationship between spatiotemporal changes of amyloid deposition and Alzheimer’s disease (AD) profiles in cognitively normal (CN) and those with mild cognitive impairment (MCI). Using a data-driven method and amyloid-PET data, we identified and validated two subtypes in two independent datasets (discovery dataset: N = 548, age = 72.4 ± 6.78, 49% female; validation dataset: N = 348, age = 74.9 ± 8.16, 47% female) from the Alzheimer’s Disease Neuroimaging Initiative across a range of individuals who were CN or had MCI. The two subtypes showed distinct regional progression patterns and presented distinct genetic, clinical and biomarker characteristics. The cortex-priority subtype was more likely to show typical clinical syndromes of symptomatic AD and vice versa. Furthermore, the regional progression patterns were associated with clinical and biomarker profiles. In sum, our findings suggest that the spatiotemporal variants of amyloid depositions are in close association with disease trajectories; these findings may provide insight into the disease monitoring and enrollment of therapeutic trials in AD.