Abstract
INTRODUCTION
We assessed TAR DNA-binding protein 43 (TDP-43) seeding activity and aggregates detection in olfactory mucosa of patients with frontotemporal lobar degeneration with TDP-43-immunoreactive pathology (FTLD-TDP) by TDP-43 seeding amplification assay (TDP43-SAA) and immunocytochemical analysis.
METHODS
The TDP43-SAA was optimized using frontal cortex samples from 16 post mortem cases with FTLD-TDP, FTLD with tau inclusions, and controls. Subsequently, olfactory mucosa samples were collected from 17 patients with FTLD-TDP, 15 healthy controls, and three patients carrying MAPT variants.
RESULTS
TDP43-SAA discriminated with 100% accuracy post mortem cases presenting or lacking TDP-43 neuropathology. TDP-43 seeding activity was detectable in the olfactory mucosa, and 82.4% of patients with FTLD-TDP tested positive, whereas 86.7% of controls tested negative (P < 0.001). Two out of three patients with MAPT mutations tested negative. In TDP43-SAA positive samples, cytoplasmatic deposits of phosphorylated TDP-43 in the olfactory neural cells were detected.
DISCUSSION
TDP-43 aggregates can be detectable in olfactory mucosa, suggesting that TDP43-SAA might be useful for identifying and monitoring FTLD-TDP in living patients.
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This post is Copyright: Elena Fontana,
Matilde Bongianni,
Alberto Benussi,
Erika Bronzato,
Carlo Scialo,
Luca Sacchetto,
Annachiara Cagnin,
Santina Castriciano,
Emanuele Buratti,
Fabrizio Gardoni,
Maria Italia,
Alberto Schreiber,
Chiara Ferracin,
Michele Fiorini,
Kathy L. Newell,
Laura Cracco,
Holly J. Garringer,
Maria Paola Cecchini,
Magdalini Polymenidou,
Alessandro Padovani,
Salvatore Monaco,
Giuseppe Legname,
Bernardino Ghetti,
Barbara Borroni,
Gianluigi Zanusso | November 1, 2023