Mattsson N, et al. - Researchers sought to develop a longitudinally valid in vivo β-amyloid (Aβ) staging system for Alzheimer disease (AD) using amyloid positron emission tomography (PET). They conducted a multicenter longitudinal cohort study and defined a 4-level staging system using fluorine 18–labeled florbetapir positron emission tomography using a combination of cerebrospinal fluid and positron emission tomography data. They included 641 participants with CSF Aβ42 data and at least two 18F-florbetapir scans; of these, 335 (52.3%) were male. The precuneus, posterior cingulate, isthmus cingulate, insula, and medial and lateral orbitofrontal cortices were the early region of Aβ accumulation. The lingual, pericalcarine, paracentral, precentral, and postcentral cortices were the late region. Remaining brain regions with increased accumulation rates were the intermediate region. As per the analysis, there was association of higher stages with lower CSF Aβ42 concentrations (from stage 1 at baseline), greater CSF P-tau (from stage 1) and CSF T-tau (from stage 2), and accelerated cognitive decline (from stage 2) and atrophy (from stage 3), even when adjusting for clinical diagnosis. Replication of the key findingswas done in the BioFINDER cohort (N = 474). When the transcriptome from the Allen Human Brain Atlas was used, differences were observed in the regions of different stages by gene expression profiles, especially involving genes associated with voltage-gated ion channel activity especially involving genes associated with voltage-gated ion channel activity, but also blood circulation, axon guidance, and lipid transportation.