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Longitudinal positron emission tomography (PET) studies of tau accumulation in Alzheimer's disease (AD) have noted reduced increases or frank decreases in tau signal. We investigated how such reductions related to analytical confounds and disease progression markers in atypical AD.    Methods  We assessed regional and interindividual variation in longitudinal change on  18 F‐flortaucipir PET imaging in 24 amyloid beta (Aβ)+ patients with atypical, early‐onset amnestic or non‐amnestic AD plus 62 Aβ– and 132 Aβ+ Alzheimer's Disease Neuroimaging Initiative (ADNI) participants.    Results  In atypical AD,  18 F‐flortaucipir uptake slowed or declined over time in areas with high baseline signal and older, more impaired individuals. ADNI participants had reduced longitudinal change in early Braak stage regions relative to late‐stage areas.    Discussion  Results suggested radioligand uptake plateaus or declines in advanced neurodegeneration. Further research should investigate whether results generalize to other radioligands and whether they relate to changes of the radioligand binding site structure or accessibility.

Rates of longitudinal change in 18 F‐flortaucipir PET vary by brain region, cognitive impairment, and age in atypical Alzheimer's disease