Association Of Tdp-43 Pathology With Global And Regional F-18-Florbetapir Pet Signal In The Alzheimer'S Disease Spectrum

Background: TAR DNA-binding protein 43 (TDP-43) has been recognized as a frequent co-pathology of Alzheimer's disease (AD). The effect of the presence of TDP-43 pathology on in vivo measures of AD-related amyloid pathology using amyloid sensitive PET is still unresolved.Objective: To study the association of TDP-43 pathology with antemortem amyloid PET signal.Methods: We studied 30 cases from the ADNI autopsy sample with available ratings of presence of TDP-43 and antemortem amyloid sensitive F-18-FlorbetapirPET. We used Bayesian regression to determine the effect of TDP-43 on global and regional amyloid PET signal. In a post-hoc analysis, we assessed the association of TDP-43 pathology with antemortem memory performance.Results: We found substantial to strong evidence for a negative effect of TDP-43 (Bayes factor against the null model (BF10 )= 9.0) and hippocampal sclerosis (BF10 = 6.4) on partial volume corrected hippocampal F-18-Florbetapir uptake. This effect was only partly mediated by the negative effect of TDP-43 on hippocampal volume. In contrast, Bayesian regression supported that there is no effect of TDP-43 on global cortical PET-signal (BF10 = 0.65). We found an anecdotal level of evidence for a negative effect of TDP-43 pathology on antemortem memory performance after accounting for global amyloid PET signal (BF10 = 1.6).Conclusion: Presence of TDP-43 pathology does not confound the global amyloid PET-signal but has a selective effect on hippocampal PET-signal that appears only partially dependent on TDP-43 mediated atrophy.