Amyloid/Tau/Neurodegeneration (ATN) image‐based biomarker trajectories of Alzheimer’s disease through 5‐year longitudinal follow‐up

Abstract

AbstractBackgroundTo investigate the progression of Alzheimer’s disease (AD) in image‐based Amyloid/Tau/Neurodegeneration (ATN) biomarkers through 5‐year longitudinal follow‐up.MethodAmong the participants who completed 18F‐florbetaben (FBB) for amyloid and 18F‐flortaucipir (FTP) for tau positron emission tomography (PET), and brain magnetic resonance (MR) imaging for neurodegeneration at a first visit, we enrolled the 145 participants who the studies at least twice [67 amyloid negative cognitive unimpaired (A‐CU), 10 amyloid positive cognitive unimpaired (A+CU), 68 amyloid positive cognitive impaired (A+CI)]. 70 participants completed the scans twice (25.2±3.1, months), and 75 participants completed the scans three times (57.9±7.4, months). We estimated the temporal trajectories of ATN biomarkers using a restricted cubic spline model and modified Euler method between baseline and annual change rates. The standardized uptake value ratio of FBB/FTP PET and hippocampal volume were used for representing each ATN biomarker, respectively.ResultThe FBB curve of the global cortex and AD‐specific regions reaches a plateau with a sigmoid appearance. FTP curves in the regions for Braak stages I‐II and III‐IV show similar sigmoid appearance while the global cortical and stage V‐VI tau curves show an exponential increase continuously. The hippocampal volume curve shows a linear decrease until the time point when the tau accumulation begins in the Braak stage I‐II, then decreases to a reversed sigmoid appearance.ConclusionLike the already known saturation of amyloid burden, it was also shown that the tau burden of the region for Braak stages I‐II and III‐IV saturated, but not in Braak stages V‐VI. Hippocampal atrophy seems to accelerate when tau begins to accumulate in early Braak stage regions. In future work, it is necessary to enroll patients at an advanced stage and collaborate with an international cohort.