Imaging tau and amyloid-β proteinopathies in Alzheimer disease and other conditions

Most neurodegenerative disorders are associated with aggregated protein deposits. In the case of Alzheimer disease (AD), extracellular amyloid-beta (A beta) aggregates and intracellular tau neurofibrillary tangles are the two neuropathological hallmarks of the disease. A beta-PET imaging has already been approved for clinical use and is being used in clinical trials of anti-A beta therapies both for patient recruitment and as an outcome measure. These studies have shown that A beta accumulation is a protracted process that can extend for more than 2 decades before the onset of clinical AD. This Review describes how in vivo brain imaging of A beta pathology has revolutionized the evaluation of patients with clinical AD by providing robust and reproducible statements of global or regional brain A beta burden and enabling the monitoring of disease progression. The role of selective tau imaging is discussed, focusing on how longitudinal tau and A beta imaging studies might reveal the various effects (sequential and/or parallel, independent and/or synergistic) of these proteins on progression, cognition and other disease-specific biomarkers of neurodegeneration. Finally, imaging studies are discussed in the context of elucidating the respective roles of A beta and tau in AD and in advancing our understanding of the relationship and/or interplay between these two proteinopathies.