Abstract
BACKGROUND
[18F] flortaucipir (FTP) binding to paired helical filament (PHF) tau in Alzheimer’s disease (AD) is well accepted. Binding to 3R and 4R tau in frontotemporal lobar degeneration (FTLD) is controversial. We aimed to investigate whether an FTP fluorescent analog (T726) can help shed light on this controversy.
METHOD
We assessed T726 binding to amyloid beta (Aβ) and different tau isoforms in nine subjects (one control, three with Alzheimer’s disease [AD], and five with FTLD) with different 3R and 4R tauopathies using fluorescence confocal microscopy.
RESULTS
T726 did not colocalize with Aβ but showed significant co-localization with PHF tau in AD. We also observed some, albeit limited, co-localization of T726 with 3R and 4R tau lesions in FTLD.
DISCUSSION
This study’s findings support FTP binding to some 3R and 4R tau lesions in FTLD. Further studies are needed to understand the biology of why FTP binds some but not all FTLD tau lesions.
Highlights

Flortaucipir analog (T726) showed significant co-localization with paired helical filament (PHF) tau in Alzheimer’s disease (AD).
Colocalization between T726 with 3R and 4R tau lesions was observed in frontotemporal lobar degeneration (FTLD).
Not all 4R tau lesions bind to T726 across different FTLD brain regions.


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This post is Copyright: Rodolfo G. Gatto,
Youssef Hossam,
R. Ross Reichard,
Val J. Lowe,
Jennifer L. Whitwell,
Keith A. Josephs | October 23, 2024

Wiley: Alzheimer’s & Dementia: Table of Contents