Utility of FDG-PET in diagnosis of Alzheimer-related TDP-43 proteinopathy
Marina Buciuc, Hugo Botha, Melissa E. Murray, Christopher G. Schwarz, Matthew L. Senjem, David T. Jones, David S. Knopman, Bradley F. Boeve, Ronald C. Petersen, Clifford R. Jack, Leonard Petrucelli, Joseph E. Parisi, Dennis W. Dickson, Val J. Lowe, Jennifer L. Whitwell, Keith A. Josephs
Abstract
OBJECTIVE: To evaluate FDG-PET as an antemortem diagnostic tool for Alzheimer-related TAR DNA-binding protein of 43 kDa (TDP-43) proteinopathy. METHODS: We conducted a cross-sectional neuroimaging-histologic analysis of patients with antemortem FDG-PET and postmortem brain tissue from the Mayo Clinic Alzheimer's Disease Research Center and Study of Aging with Alzheimer spectrum pathology. TDP-43-positive status was assigned when TDP-43-immunoreactive inclusions were identified in the amygdala. Statistical parametric mapping (SPM) analyses compared TDP-43-positive (TDP-43[+]) with TDP-43-negative cases (TDP-43[-]), correcting for field strength, sex, Braak neurofibrillary tangle, and neuritic plaque stages. Cross-validated logistic regression analyses were used to determine whether regional FDG-PET values predict TDP-43 status. We also assessed the ratio of inferior temporal to medial temporal (IMT) metabolism as this was proposed as a biomarker of hippocampal sclerosis. RESULTS: < 0.001). An IMT/FSO ratio was superior to the IMT in discriminating TDP-43(+) cases: 78% vs 48%, respectively. CONCLUSIONS: Alzheimer-related TDP-43 proteinopathy is associated with hypometabolism in the medial temporal and frontal regions. Combining FDG-PET measures from these regions may be useful for antemortem prediction of Alzheimer-related TDP-43 proteinopathy. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that hypometabolism in the medial temporal and frontal regions on FDG-PET is associated with Alzheimer-related TDP-43 proteinopathy.