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These authors investigated the relationship between amyloid-β, phosphorylated tau, and apolipoprotein E in preclinical Alzheimer disease in 170 patients and controls who had serial imaging up to 3.5 years after the initial study. Global volumes as well as volumes in brain regions known to be involved in the chronic stages of the disease were assessed. Their results led them to propose that atrophy rates are primarily influenced by apolipoprotein E via amyloid-β mechanisms and that amyloid-β -associated neurodegeneration occurs only in the presence of phosphorylated tau.