Affiliations: [a]
German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany
| [b]
Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany
| [c] Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain
Correspondence:
[*]
Correspondence to: Stefan J. Teipel, MD, Department of Psychosomatic Medicine, University Medicine Rostock, and DZNE Rostock, Gehlsheimer Str. 20, 18147 Rostock, Germany. Tel.: +01149 381 494 9470; Fax: +01149 381 494 9682; E-mail: [email protected]. and Michel J. Grothe, PhD, Unidad de Tra-stornos del Movimiento, Instituto de Biomedicina de Sevilla (IB iS), Avda. Manuel Siurot s/n, 41013 Seville, Spain. Tel.:+34 955 923 000; Fax:+34 955 923 101; E-mail: [email protected].
Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu/). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf
Abstract: 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 18F-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 18F-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.
Keywords: Amyloid pathology, florbetapir PET, hippocampal sclerosis, hippocampal volume, memory, TAR DNA-binding protein 43
