IMPORTANCE Biomarkers for chronic traumatic encephalopathy (CTE) are currently lacking. The radiotracer fluorine F 18-labeled ( 18 F)-flortaucipir (FTP) detects tau pathology in Alzheimer disease, and positron emission tomography (PET) with FTP shows elevated binding in individuals at risk for CTE. No study, however, has assessed the correlation between in vivo FTP PET and postmortem tau in CTE.OBJECTIVE To assess the regional association between in vivo FTP binding and postmortem tau pathology in a patient with pathologically confirmed CTE. DESIGN, SETTING, AND PARTICIPANTSA white male former National Football League player with 17 years of US football exposure was clinically diagnosed with traumatic encephalopathy syndrome at a neurology tertiary referral center. 18 F-Fludeoxyglucose, carbon 11-labeled Pittsburgh compound B, and FTP PET were performed 52 months prior to death, and magnetic resonance imaging, 50 months prior to death. Brain images were assessed qualitatively for abnormalities blinded to autopsy data. Autopsy was performed using a neurodegenerative research protocol. The FTP standardized uptake value ratios (inferior cerebellar gray reference region) and W-score (age-adjusted z-score) maps were compared with phosphorylated tau immunohistochemical analysis with monoclonal antibody CP13. MAIN OUTCOMES AND MEASURESQualitative and quantitative comparisons between antemortem FTP PET and tau pathology at autopsy. RESULTSFlortaucipir uptake was distributed in a patchy, frontotemporal-predominant pattern that overlapped with regions showing neurodegeneration on magnetic resonance imaging and hypometabolism on 18 F-fludeoxyglucose PET. Pathological assessment revealed stage 4 CTE; limbic argyrophilic grain disease; stage 2 limbic-predominant, age-related transactive response DNA-binding protein 43 encephalopathy; and Braak neurofibrillary tangle stage 3. 18 F-Flortaucipir W-maps matched areas of high postmortem tau burden in left fusiform and inferior temporal gyri and juxtacortical frontal white matter. High FTP W-scores with low tau burden were found in the basal ganglia, thalamus, motor cortex, and calcarine cortex. No regions with low FTP W-scores corresponded to areas with high pathological tau burden. A modest correlation, which did not reach statistical significance (ρ = 0.35, P = .17), was found between FTP standardized uptake value ratio and tau area fraction at the regional level. CONCLUSIONS AND RELEVANCEIn this patient, FTP PET findings during life showed a modest correspondence with postmortem pathology in CTE. These findings suggest that FTP may have limited utility as a tau biomarker in CTE.

We present an efficient first-principles method for simulating noncontact atomic force microscopy (nc-AFM) images using a "frozen density" embedding theory. Frozen density embedding theory enables one to efficiently compute the tip-sample interaction by considering a sample as a frozen external field. This method reduces the extensive computational load of first-principles AFM simulations by avoiding consideration of the entire tip-sample system and focusing on the tip alone. We demonstrate that our simulation with frozen density embedding theory accurately reproduces full density functional theory simulations of freestanding hydrocarbon molecules while the computational time is significantly reduced. Our method also captures the electronic effect of a Cu(111) substrate on the AFM image of pentacene and reproduces the experimental AFM image of Cu2N on a Cu(100) surface. This approach is applicable for theoretical imaging applications on large molecules, two-dimensional materials, and materials surfaces.

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