With the recent approval of 18F-flortaucipir (previously called T807/AV-1451, trade name Tauvid; Lilly) for clinical use by the US Food and Drug Administration, there is increasing excitement around tau imaging. 18F-flortaucipir PET is now approved to estimate the density and distribution of aggregated tau neurofibrillary tangles in adults with cognitive impairment undergoing evaluation for Alzheimer’s disease (AD)(1). The Food and Drug Administration approval was based on evidence that visual interpretations of 18F-flortaucipir PET showed high sensitivity and specificity for advanced-stage tau pathology as determined at autopsy (2). In addition to its diagnostic use, tau PET can image the spatiotemporal progression of tau pathology in longitudinal studies, shining a light on the central role of tau in driving neurodegeneration and cognitive decline throughout the insidious evolution of AD.

Tau is a microtubule binding protein that plays an important physiologic role in axonal transport, cytoskeletal architecture, and membrane-based signaling pathways (3). In humans, tau undergoes alternative splicing to form 6 isoforms, each of which contains either 3 or 4 repeat microtubule binding motifs (3R or 4R isoforms). In neurodegenerative diseases, tau undergoes abnormal phosphorylation and acetylation, causing it to disassemble from microtubules and form fibrillar insoluble aggregates that propagate through the brain. In AD, aggregated forms of tau are found in dystrophic neurites around amyloid-b plaques and in neurofibrillary tangles that consist of mixed 3R/4R tau isoforms that form paired helical filaments. 18F-flortaucipir, the first and most widely studied tau-specific radiotracer, is specific to the tau aggregates of AD and shows absent-to-low binding in non-AD tauopathies. Autopsy studies have shown that neurofibrillary tangles follow a stereotypical progression from transentorhinal (Braak stages I/II) to limbic (Braak III/IV) and finally neocortical (Braak V/VI) regions. Tau PET patterns reported with 18F-flortaucipir and other tau radiotracers generally reproduce the expected topography of neuropathologic Braak staging (4). AD neuropathologic changes are measured based on the distribution of both amyloid and tau pathology. The relationship between AD neuropathologic changes and clinical state is