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ARUK 2023 | Why does tau-PET not detect the earliest stages of Alzheimer’s disease?

The importance of accurate visualization, mapping, and quantification of tau neurofibrillary tangles in Alzheimer’s disease has become increasingly recognized in recent years, as studies have shown neurodegeneration and cognitive impairment to associate more strongly with tau burden than amyloid plaques. Tau-PET radiotracers have contributed significantly to our ability to do this, but remain limited by off-target binding, limited detection in the earliest stages of disease, and lack of validation of visual assessment routines. Michael Schöll, PhD, University of Gothenburg, Gothenburg, Sweden, discusses the findings of imaging-neuropathology validation studies aiming to characterize the properties of current PET tracers. Studies have shown that [18F]flortaucipir PET does not give a positive signal until patients reach Braak stage IV. The temporal delay means that a PET-derived Braak stage actually reflects a past neuropathologic Braak stage and tau pathology may have already spread. Prof. Schöll explains how the dynamics of tau accumulation likely contribute to this difference, with spreading predominating in the early Braak stages rather than local replication, keeping tau density too low for PET detection. This interview took place at the Alzheimer’s Research UK (ARUK) Conference 2023 in Aberdeen, UK.

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Michael Schöll reports the following disclosures: scientific advisory boards for Roche, NovoNordisk and Servier.