FLORTAUCIPIR TAU-PET SPECIFICITY IS MAINTAINED IN PATIENTS WITH PATHOLOGICALLY CONFIRMED CREUTZFELDT-JAKOB DISEASE

Abstract

[18F]AV-1451 (Flortaucipir) exhibits good specificity for binding neurofibrillary tangles (NFTs) in Alzheimer disease (AD). It is unknown whether this specificity is maintained in neurodegenerative diseases associated with profound neuronal lysis and elevations in soluble tau (i.e. Creutzfeldt-Jakob disease; CJD). [18F]AV-1451 PET neuroimaging was performed in 5 consecutive patients who presented with sporadic Creutzfeldt-Jakob disease (CJD). At autopsy, patients were evaluated for AD neuropathologic change (ADNC) and CJD (CJD subtyping performed by the National Prion Disease Pathology Surveillance Center, Case Western University; Cleveland, Ohio). Tauopathy was quantified by study authors blinded to imaging findings using anti-phosphorylated tau (PHF1) immunohistochemistry. [18F]AV-1451 retention was compared between CJD patients (median age, 66 [63–74] years) and amyloid-beta-negative cognitively normal (CN) controls (n=44; median age, 68 [63–74] years), and participants with very mild AD dementia (n=8; median age, 77 [63–90]). All CJD patients presented with rapidly progressive dementia leading to death within 9 months of symptom onset. The median interval from [18F]AV-1451 PET to autopsy was 4 (1–14) weeks. Restricted diffusion within the cortical ribbon and/or deep-gray structures, and elevations of CSF tau (median=6519; range=1528–13240 pg/mL) were observed in all cases, suggestive of rapid neuronal loss. No unique pattern of 18F-AV1451 retention was observed on visual inspection. Standardized uptake value ratios (SUVRs; referenced to cerebellar cortex; partial volume corrected) were summarized across known regions that are often affected in symptomatic AD dementia (i.e., amygdala, entorhinal, inferotemporal, and lateral occipital cortices). Summary SUVRs in CJD patients (1.17, 1.08–1.36) were indistinguishable from those observed in CN controls (1.14, 0.84–1.54; p=0.6), and well below levels measured in AD participants (2.23, 1.60–3.04; p=<0.01). Focal [18F]AV-1451 retention was observed within the temporal lobes of one CJD patient (1.45 standard units above the mean observed in CN controls; p=0.15; Fig. 1A). Microscopy demonstrated a moderately dense focus of NFTs within the temporal isocortex, in the context of Braak NFT stage I and low-level ADNC (A1B1C0; NIA-AA criteria). Flortaucipir retention was not seen in another case (Fig. 1B) with Braak NFT stage III and intermediate-level ADNC (A2B2C1/2).