Induction of amyloid-β deposits from serially transmitted, histologically silent, Aβ seeds issued from human brains - Molecular Imaging Research Center Accéder directement au contenu
Article Dans Une Revue Acta Neuropathologica Communications Année : 2020

Induction of amyloid-β deposits from serially transmitted, histologically silent, Aβ seeds issued from human brains

Franck Letournel
  • Fonction : Collaborateur
Marie-Laure Martin-Negrier
  • Fonction : Collaborateur
Maxime Faisant
  • Fonction : Collaborateur
Catherine Godfraind
  • Fonction : Collaborateur
Claude-Alain Maurage
  • Fonction : Collaborateur
Vincent Deramecourt
  • Fonction : Collaborateur
Mathilde Duchesne
  • Fonction : Collaborateur
David Meyronnet
  • Fonction : Collaborateur
André Maues de Paula
  • Fonction : Collaborateur
Fanny Burel-Vandenbos
  • Fonction : Collaborateur
Charles Duyckaerts
  • Fonction : Collaborateur
Danielle Seilhean
  • Fonction : Collaborateur
Isabelle Plu
Serge Milin
  • Fonction : Collaborateur
  • PersonId : 922943
Dan Christian Chiforeanu
  • Fonction : Collaborateur
Annie Laquerriere
  • Fonction : Collaborateur
Béatrice Lannes
  • Fonction : Collaborateur

Résumé

In humans, iatrogenic transmission of cerebral amyloid-β (Aβ)-amyloidosis is suspected following inoculation of pituitary-derived hormones or dural grafts presumably contaminated with Aβ proteins as well as after cerebral surgeries. Experimentally, intracerebral inoculation of brain homogenate extracts containing misfolded Aβ can seed Aβ deposition in transgenic mouse models of amyloidosis or in non-human primates. The transmission of cerebral Aβ is governed by the host and by the inoculated samples. It is critical to better characterize the propensities of different hosts to develop Aβ deposition after contamination by an Aβ-positive sample as well as to better assess which biological samples can transmit this lesion. Aβ precursor protein (huAPP wt) mice express humanized non-mutated forms of Aβ precursor protein and do not spontaneously develop Aβ or amyloid deposits. We found that inoculation of Aβ-positive brain extracts from Alzheimer patients in these mice leads to a sparse Aβ deposition close to the alveus 18 months post-inoculation. However, it does not induce cortical or hippocampal Aβ deposition. Secondary inoculation of apparently amyloid deposit-free hippocampal extracts from these huAPP wt mice to APP swe /PS1 dE9 mouse models of amyloidosis enhanced Aβ deposition in the alveus 9 months post-inoculation. This suggests that Aβ seeds issued from human brain samples can persist in furtive forms in brain tissues while maintaining their ability to foster Aβ deposition in receptive hosts that overexpress endogenous Aβ. This work emphasizes the need for high-level preventive measures, especially in the context of neurosurgery, to prevent the risk of iatrogenic transmission of Aβ lesions from samples with sparse amyloid markers.

Domaines

Neurobiologie
Fichier principal
Vignette du fichier
Herard-ActaNeuropatholCom-2020.pdf (1.56 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03052986 , version 1 (10-12-2020)

Identifiants

Citer

Anne-Sophie Herard, Fanny Petit, Charlotte Gary, Martine Guillermier, Susana Boluda, et al.. Induction of amyloid-β deposits from serially transmitted, histologically silent, Aβ seeds issued from human brains. Acta Neuropathologica Communications, 2020, 8 (1), ⟨10.1186/s40478-020-01081-7⟩. ⟨hal-03052986⟩
71 Consultations
88 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More