Amyloid Beta Clearance in Alzheimer’s Disease: A PET Imaging and Data Science Study

Amyloid beta (Aβ), a byproduct of amyloid precursor protein, is constantly cleared from the CNS. Aβ kinetics are visualized using 18F-florbetapir PET imaging, typically analyzed through 2D coregistration with MRI or CT followed by visual evaluation. Aβ was thought to coexist in the white matter of both Alzheimer’s disease (AD; Aβ+) patients and cognitively unimpaired (CU; Aβ-) individuals. However, this coexistence is likely a misperception of 2D imaging. In this study, data science techniques were used to evaluate PET images, transforming Aβ imaging into topographical pixel arrays for 3D reconstruction. Canal-like networks in the brain, skull, and neck were discovered to be part of the non-CNS fluid (NCF) compartment, which quarantines Aβ. In CU/Aβ- subjects, Aβ is transported to peripheral lymphatics. In AD/Aβ+ subjects, Aβ becomes congested in the NCF, diffusing into CNS interstitial fluid, leading to progression and neurodegeneration.