¹⁸F-Flortaucipir in TDP-43 associated frontotemporal dementia

Area of Science:

• Neuroimaging
• Neuropathology
• Molecular Biology

Background:

• ¹⁸F-Flortaucipir retention is elevated in semantic variant primary progressive aphasia (svPPA), a condition linked to TDP-43 pathology.
• The behavior of ¹⁸F-Flortaucipir in other TDP-43 proteinopathies, like C9orf72 expansion-associated frontotemporal dementia (bvFTD), remains unclear.

Purpose of the Study:

• To investigate ¹⁸F-Flortaucipir retention in C9orf72 expansion carriers and svPPA patients.
• To determine if ¹⁸F-Flortaucipir binding is a general indicator of TDP-43 pathology.

Main Methods:

• ¹⁸F-Flortaucipir PET and MRI scans were performed on C9orf72 expansion carriers (n=6), svPPA patients (n=6), and healthy controls (n=54).
• Alzheimer's Disease (AD) patient data (n=39) were used for comparison.
• Region-of-interest (ROI) and voxel-level analyses were conducted, supplemented by ³H-Flortaucipir autoradiography.

Main Results:

• SvPPA patients showed increased bilateral lateral temporal cortex ¹⁸F-Flortaucipir retention, though less than in AD dementia.
• C9orf72 patients had minimal or no significant ¹⁸F-Flortaucipir retention in voxel-based analysis, with only slight increases in the inferior frontal lobes in ROI analysis.
• Autoradiography revealed no specific ³H-Flortaucipir binding in either svPPA or C9orf72 cases.

Conclusions:

• Temporal lobe ¹⁸F-Flortaucipir retention occurs in some svPPA cases but is less pronounced than in AD.
• ¹⁸F-Flortaucipir binding is not a general characteristic of TDP-43 proteinopathies, as evidenced by the lack of significant retention in C9orf72 mutation carriers.