Utility of FDG-PET in diagnosis of Alzheimer-related TDP-43 proteinopathy.

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:

Of 73 cases, 27 (37%) were TDP-43(+), of which 6 (8%) had hippocampal sclerosis. SPM analysis showed TDP-43(+) cases having greater hypometabolism of medial temporal, frontal superior medial, and frontal supraorbital (FSO) regions (p unc < 0.001). Logistic regression analysis showed only FSO and IMT to be associated with TDP-43(+) status, identifying up to 81% of TDP-43(+) cases (p < 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.

• Authors: 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 Jr, Leonard Petrucelli, Joseph E Parisi, Dennis W Dickson, Val Lowe, Jennifer L Whitwell, Keith A Josephs
• Journal: Neurology (Neurology) Vol. 95 Issue 1 Pg. e23-e34 (07 07 2020) ISSN: 1526-632X [Electronic] United States
• PMID: 32518145 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2020 American Academy of Neurology.

Chemical References

• Radiopharmaceuticals
• Fluorodeoxyglucose F18

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (complications)
• Cross-Sectional Studies
• Female
• Fluorodeoxyglucose F18
• Humans
• Male
• Neuroimaging (methods)
• Positron-Emission Tomography (methods)
• Radiopharmaceuticals
• Retrospective Studies
• TDP-43 Proteinopathies (diagnostic imaging, etiology)