Human subiculo-fornico-mamillary system ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
Human subiculo-fornico-mamillary system in alzheimer''s disease: tau seeding by the pillar of the fornix
Auteur(s) :
Thierry, Manon [Auteur]
Boluda, Susana [Auteur]
Delatour, Benoit [Auteur]
Marty, Serge [Auteur]
Seilhean, Danielle [Auteur]
Potier, Marie-Claude [Auteur]
Duyckaerts, Charles [Auteur]
Boluda, Susana [Auteur]
Delatour, Benoit [Auteur]
Marty, Serge [Auteur]
Seilhean, Danielle [Auteur]
Potier, Marie-Claude [Auteur]
Duyckaerts, Charles [Auteur]
Titre de la revue :
Acta neuropathologica
Nom court de la revue :
Acta Neuropathol.
Date de publication :
2019-12-10
ISSN :
1432-0533
Mot(s)-clé(s) :
Biosensor
Alzheimer''s disease
Propagation
Seeding
Subiculo-fornico-mamillary system
Abeta
Axon propagation
Electron microscopy
CLARITY
Microcryodissection
Tau
Alzheimer''s disease
Propagation
Seeding
Subiculo-fornico-mamillary system
Abeta
Axon propagation
Electron microscopy
CLARITY
Microcryodissection
Tau
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
In Alzheimer's disease (AD), Tau and Aβ aggregates involve sequentially connected regions, sometimes distantly separated. These alterations were studied in the pillar of the fornix (PoF), an axonal tract, to analyse the ...
Lire la suite >In Alzheimer's disease (AD), Tau and Aβ aggregates involve sequentially connected regions, sometimes distantly separated. These alterations were studied in the pillar of the fornix (PoF), an axonal tract, to analyse the role of axons in their propagation. The PoF axons mainly originate from the subicular neurons and project to the mamillary body. Forty-seven post-mortem cases at various Braak stages (Tau) and Thal phases (Aβ) were analysed by immunohistochemistry. The distribution of the lesions showed that the subiculum was affected before the mamillary body, but neither Tau aggregation nor Aβ deposition was consistently first. The subiculum and the mamillary body contained Gallyas positive neurofibrillary tangles, immunolabelled by AT8, TG3, PHF1, Alz50 and C3 Tau antibodies. In the PoF, only thin and fragmented threads were observed, exclusively in the cases with neurofibrillary tangles in the subiculum. The threads were made of Gallyas negative, AT8 and TG3 positive Tau. They were intra-axonal and devoid of paired helical filaments at electron microscopy. We tested PoF homogenates containing Tau AT8 positive axons in a Tau P301S biosensor HEK cell line and found a seeding activity. There was no Aβ immunoreactivity detected in the PoF. We could follow microcryodissected AT8 positive axons entering the mamillary body; contacts between Tau positive endings and Aβ positive diffuse or focal deposits were observed in CLARITY-cleared mamillary body. In conclusion, we show that non-fibrillary, hyperphosphorylated Tau is transported by the axons of the PoF from the subiculum to the mamillary body and has a seeding activity. Either Tau aggregation or Aβ accumulation may occur first in this system: this inconstant order is incompatible with a cause-and-effects relationship. However, both pathologies were correlated and intimately associated, indicating an interaction of the two processes, once initiated.Lire moins >
Lire la suite >In Alzheimer's disease (AD), Tau and Aβ aggregates involve sequentially connected regions, sometimes distantly separated. These alterations were studied in the pillar of the fornix (PoF), an axonal tract, to analyse the role of axons in their propagation. The PoF axons mainly originate from the subicular neurons and project to the mamillary body. Forty-seven post-mortem cases at various Braak stages (Tau) and Thal phases (Aβ) were analysed by immunohistochemistry. The distribution of the lesions showed that the subiculum was affected before the mamillary body, but neither Tau aggregation nor Aβ deposition was consistently first. The subiculum and the mamillary body contained Gallyas positive neurofibrillary tangles, immunolabelled by AT8, TG3, PHF1, Alz50 and C3 Tau antibodies. In the PoF, only thin and fragmented threads were observed, exclusively in the cases with neurofibrillary tangles in the subiculum. The threads were made of Gallyas negative, AT8 and TG3 positive Tau. They were intra-axonal and devoid of paired helical filaments at electron microscopy. We tested PoF homogenates containing Tau AT8 positive axons in a Tau P301S biosensor HEK cell line and found a seeding activity. There was no Aβ immunoreactivity detected in the PoF. We could follow microcryodissected AT8 positive axons entering the mamillary body; contacts between Tau positive endings and Aβ positive diffuse or focal deposits were observed in CLARITY-cleared mamillary body. In conclusion, we show that non-fibrillary, hyperphosphorylated Tau is transported by the axons of the PoF from the subiculum to the mamillary body and has a seeding activity. Either Tau aggregation or Aβ accumulation may occur first in this system: this inconstant order is incompatible with a cause-and-effects relationship. However, both pathologies were correlated and intimately associated, indicating an interaction of the two processes, once initiated.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
CHU Lille
Inserm
Université de Lille
Inserm
Université de Lille
Collections :
Équipe(s) de recherche :
Alzheimer et Tauopathies
Développement et plasticité du cerveau neuro-endocrine
Développement et plasticité du cerveau neuro-endocrine
Date de dépôt :
2021-06-23T13:45:11Z