Contributors: Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN); Molecular Imaging Research Center Fontenay-aux-Roses (MIRCEN); Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB); Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS); Université Paris-Saclay; CEA- Saclay (CEA); Commissariat à l'énergie atomique et aux énergies alternatives (CEA); Institut du Cerveau = Paris Brain Institute (ICM); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS); CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Excellence Laboratory LabEx DISTALZ; Université de Lille; Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Fonctionnement et Dysfonctionnement Cognitifs : Les âges de la vie (DysCo); Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN); Brain Bank Neuro-C. E. B. Neuropathology Network: Franck Letournel, Marie-Laure Martin-Négrier, Maxime Faisant, Catherine Godfraind, Jean Boutonnat, Claude-Alain Maurage, Vincent Deramecourt, Mathilde Duchesne, David Meyronet, Tanguy Fenouil, André Mauès de Paula, Valérie Rigau, Fanny Vandenbos-Burel, Danielle Seilhean, Charles Duyckaerts, Susana Boluda, Isabelle Plu, Dan Christian Chiforeanu, Annie Laquerrière, Florent Marguet, Béatrice Lannes, Benoît Lhermitte; ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011)
نبذة مختصرة : International audience ; Abstract Amyloid-β (Aβ) pathology transmission has been described in patients following iatrogenic exposure to compounds contaminated with Aβ proteins. It can induce cerebral Aβ angiopathy resulting in brain hemorrhages and devastating clinical impacts. Iatrogenic transmission of tau pathology is also suspected but not experimentally proven. In both scenarios, lesions were detected several decades after the putatively triggering medico-surgical act. There is however little information regarding the cognitive repercussions in individuals who do not develop cerebral hemorrhages. In the current study, we inoculated the posterior cingulate cortex and underlying corpus callosum of young adult primates ( Microcebus murinus ) with either Alzheimer’s disease or control brain extracts. This led to widespread Aβ and tau pathologies in all of the Alzheimer-inoculated animals following a 21-month-long incubation period (n = 12) whereas none of the control brain extract-inoculated animals developed such lesions (n = 6). Aβ deposition affected almost all cortical regions. Tau pathology was also detected in Aβ-deposit-free regions distant from the inoculation sites ( e.g. in the entorhinal cortex), while some regions adjacent, but not connected, to the inoculation sites were spared ( e.g. the occipital cortex). Alzheimer-inoculated animals developed cognitive deficits and cerebral atrophy compared to controls. These pathologies were induced using two different batches of Alzheimer brain extracts. This is the first experimental demonstration that tau can be transmitted by human brain extracts inoculations in a primate. We also showed for the first time that the transmission of widespread Aβ and tau pathologies can be associated with cognitive decline. Our results thus reinforce the need to organize a systematic monitoring of individuals who underwent procedures associated with a risk of Aβ and tau iatrogenic transmission. They also provide support for Alzheimer brain-inoculated primates as relevant ...
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