Author response: In vivo [18F]-AV-1451 tau-PET imaging in sporadic Creutzfeldt-Jakob disease.

Abstract

As summarized by Drs. Yuan and Hu, the distribution of “tau pathologies” did not reflect the deposition of prion protein in the 5 patients with sporadic Creutzfeldt-Jakob disease (sCJD) included in our study.1 However, the evidence supporting this statement comes from direct neuropathologic analysis (not described in detail in this article), rather than from [18F]-AV-1451 (tau) PET neuroimaging. Of interest, although low-to-intermediate level Alzheimer disease (AD) neuropathologic change was identified in all patients with autopsy-proven sCJD, [18F]-AV-1451 PET retention was not increased in any brain region in sCJD cases vs amyloid ([18F]-AV-45)–negative cognitively normal controls. Thus, while our findings suggest that [18F]-AV-1451 PET specificity for AD-associated paired-helical filaments was not compromised by brain changes attributable to sCJD, tracer sensitivity to lower levels of AD-associated tau pathology likely limited our ability to consider the relationship between [18F]-AV-1451 retention and prion protein deposition. We agree that other advanced neuroimaging techniques, including fluorodeoxyglucose PET and magnetic resonance diffusion-weighted imaging,2–4 may be more sensitive to the neuronal dysfunction and degeneration that characterizes sCJD. These measures may be used in combination with [18F]-AV-1451 PET imaging to distinguish patients with symptoms attributable to sCJD from other, more common, neurodegenerative dementing illnesses, including symptomatic AD.5