  Three major biomarkers: beta-amyloid (A), pathologic tau (T), and
neurodegeneration (N), are recognized as valid proxies for neuropathologic
changes of Alzheimer's disease. While there are extensive studies on
cerebrospinal fluids biomarkers (amyloid, tau), the spatial propagation pattern
across brain is missing and their interactive mechanisms with neurodegeneration
are still unclear. To this end, we aim to analyze the spatiotemporal
associations between ATN biomarkers using large-scale neuroimaging data. We
first investigate the temporal appearances of amyloid plaques, tau tangles, and
neuronal loss by modeling the longitudinal transition trajectories. Second, we
propose linear mixed-effects models to quantify the pathological interactions
and propagation of ATN biomarkers at each brain region. Our analysis of the
current data shows that there exists a temporal latency in the build-up of
amyloid to the onset of tau pathology and neurodegeneration. The propagation
pattern of amyloid can be characterized by its diffusion along the topological
brain network. Our models provide sufficient evidence that the progression of
pathological tau and neurodegeneration share a strong regional association,
which is different from amyloid.
