Detection of TDP-43 seeding activity in the olfactory mucosa from patients with frontotemporal dementia.
TAR DNA-binding protein 43
frontotemporal dementia
frontotemporal lobar degeneration
olfactory mucosa
seeding
seeding amplification assays
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
31 Oct 2023
31 Oct 2023
Historique:
revised:
10
10
2023
received:
25
07
2023
accepted:
11
10
2023
medline:
1
11
2023
pubmed:
1
11
2023
entrez:
1
11
2023
Statut:
aheadofprint
Résumé
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. 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. 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. 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.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIA NIH HHS
ID : P30 AG010133
Pays : United States
Informations de copyright
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
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