Spatiotemporal Distribution of ß-Amyloid in Alzheimer Disease Is the Result of Heterogeneous Regional Carrying Capacities.

ABSTRACT

ß-amyloid (Aß) accumulation in the brain is 1 of 2 pathologic hallmarks of Alzheimer disease (AD), and the spatial distribution of Aß has been studied extensively ex vivo. Methods: We applied mathematical modeling to Aß in vivo PET imaging data to investigate competing theories of Aß spread in AD. Results: Our results provided evidence that Aß accumulation starts in all brain regions simultaneously and that its spatiotemporal distribution is due to heterogeneous regional carrying capacities (regional maximum possible concentration of Aß) for the aggregated protein rather than to longer-term spreading from seed regions. Conclusion: The in vivo spatiotemporal distribution of Aß in AD can be mathematically modeled using a logistic growth model in which the Aß carrying capacity is heterogeneous across the brain but the exponential growth rate and time of half maximal Aß concentration are constant.