Cargando…

Pathological changes induced by Alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice

Alzheimer's disease (AD) is characterized by intracerebral accumulations of extracellular amyloid-β (Aβ) plaques and intracellular tau pathology that spread in the brain. Three types of tau lesions occur in the form of neuropil threads, neurofibrillary tangles, and neuritic plaques i.e. tau agg...

Descripción completa

Detalles Bibliográficos
Autores principales: Lam, Suzanne, Hérard, Anne-Sophie, Boluda, Susana, Petit, Fanny, Eddarkaoui, Sabiha, Cambon, Karine, Picq, Jean-Luc, Buée, Luc, Duyckaerts, Charles, Haïk, Stéphane, Dhenain, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9380345/
https://www.ncbi.nlm.nih.gov/pubmed/35974399
http://dx.doi.org/10.1186/s40478-022-01410-y
_version_ 1784768866847555584
author Lam, Suzanne
Hérard, Anne-Sophie
Boluda, Susana
Petit, Fanny
Eddarkaoui, Sabiha
Cambon, Karine
Picq, Jean-Luc
Buée, Luc
Duyckaerts, Charles
Haïk, Stéphane
Dhenain, Marc
author_facet Lam, Suzanne
Hérard, Anne-Sophie
Boluda, Susana
Petit, Fanny
Eddarkaoui, Sabiha
Cambon, Karine
Picq, Jean-Luc
Buée, Luc
Duyckaerts, Charles
Haïk, Stéphane
Dhenain, Marc
author_sort Lam, Suzanne
collection PubMed
description Alzheimer's disease (AD) is characterized by intracerebral accumulations of extracellular amyloid-β (Aβ) plaques and intracellular tau pathology that spread in the brain. Three types of tau lesions occur in the form of neuropil threads, neurofibrillary tangles, and neuritic plaques i.e. tau aggregates within neurites surrounding Aβ deposits. The cascade of events linking these lesions and synaptic or memory impairments are still debated. Intracerebral infusion of human AD brain extracts in Aβ plaque-bearing mice that do not overexpress pathological tau proteins induces tau pathologies following heterotopic seeding of mouse tau protein. There is however little information regarding the downstream events including synaptic or cognitive repercussions of tau pathology induction in these models. In the present study, human AD brain extracts (AD(be)) and control-brain extracts (Ctrl(be)) were infused into the hippocampus of Aβ plaque-bearing APP(swe)/PS1(dE9) mice. Memory, synaptic density, as well as Aβ plaque and tau aggregate loads, microgliosis, astrogliosis at the inoculation site and in connected regions (perirhinal/entorhinal cortex) were evaluated 4 and 8 months post-inoculation. AD(be) inoculation produced the following effects: (i) memory deficit; (ii) increased Aβ plaque deposition in proximity to the inoculation site; (iii) tau pathology induction; (iv) appearance of neuropil threads and neurofibrillary tangles next to the inoculation site with a spreading to connected regions. Neuritic plaque pathology was detected in both AD(be)- and Ctrl(be)-inoculated animals but AD(be) inoculation increased the severity close to and at distance of the inoculation site. (v) Finally, AD(be) inoculation reduced synaptic density in the vicinity to the inoculation site and in connected regions as the perirhinal/entorhinal cortex. Synaptic impairments were correlated with increased severity of neuritic plaques but not to other tau lesions or Aβ lesions, suggesting that neuritic plaques are a culprit for synaptic loss. Synaptic density was also associated with microglial load. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-022-01410-y.
format Online
Article
Text
id pubmed-9380345
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-93803452022-08-17 Pathological changes induced by Alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice Lam, Suzanne Hérard, Anne-Sophie Boluda, Susana Petit, Fanny Eddarkaoui, Sabiha Cambon, Karine Picq, Jean-Luc Buée, Luc Duyckaerts, Charles Haïk, Stéphane Dhenain, Marc Acta Neuropathol Commun Research Alzheimer's disease (AD) is characterized by intracerebral accumulations of extracellular amyloid-β (Aβ) plaques and intracellular tau pathology that spread in the brain. Three types of tau lesions occur in the form of neuropil threads, neurofibrillary tangles, and neuritic plaques i.e. tau aggregates within neurites surrounding Aβ deposits. The cascade of events linking these lesions and synaptic or memory impairments are still debated. Intracerebral infusion of human AD brain extracts in Aβ plaque-bearing mice that do not overexpress pathological tau proteins induces tau pathologies following heterotopic seeding of mouse tau protein. There is however little information regarding the downstream events including synaptic or cognitive repercussions of tau pathology induction in these models. In the present study, human AD brain extracts (AD(be)) and control-brain extracts (Ctrl(be)) were infused into the hippocampus of Aβ plaque-bearing APP(swe)/PS1(dE9) mice. Memory, synaptic density, as well as Aβ plaque and tau aggregate loads, microgliosis, astrogliosis at the inoculation site and in connected regions (perirhinal/entorhinal cortex) were evaluated 4 and 8 months post-inoculation. AD(be) inoculation produced the following effects: (i) memory deficit; (ii) increased Aβ plaque deposition in proximity to the inoculation site; (iii) tau pathology induction; (iv) appearance of neuropil threads and neurofibrillary tangles next to the inoculation site with a spreading to connected regions. Neuritic plaque pathology was detected in both AD(be)- and Ctrl(be)-inoculated animals but AD(be) inoculation increased the severity close to and at distance of the inoculation site. (v) Finally, AD(be) inoculation reduced synaptic density in the vicinity to the inoculation site and in connected regions as the perirhinal/entorhinal cortex. Synaptic impairments were correlated with increased severity of neuritic plaques but not to other tau lesions or Aβ lesions, suggesting that neuritic plaques are a culprit for synaptic loss. Synaptic density was also associated with microglial load. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-022-01410-y. BioMed Central 2022-08-16 /pmc/articles/PMC9380345/ /pubmed/35974399 http://dx.doi.org/10.1186/s40478-022-01410-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Lam, Suzanne
Hérard, Anne-Sophie
Boluda, Susana
Petit, Fanny
Eddarkaoui, Sabiha
Cambon, Karine
Picq, Jean-Luc
Buée, Luc
Duyckaerts, Charles
Haïk, Stéphane
Dhenain, Marc
Pathological changes induced by Alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice
title Pathological changes induced by Alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice
title_full Pathological changes induced by Alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice
title_fullStr Pathological changes induced by Alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice
title_full_unstemmed Pathological changes induced by Alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice
title_short Pathological changes induced by Alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice
title_sort pathological changes induced by alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9380345/
https://www.ncbi.nlm.nih.gov/pubmed/35974399
http://dx.doi.org/10.1186/s40478-022-01410-y
work_keys_str_mv AT lamsuzanne pathologicalchangesinducedbyalzheimersbraininoculationinamyloidbetaplaquebearingmice
AT herardannesophie pathologicalchangesinducedbyalzheimersbraininoculationinamyloidbetaplaquebearingmice
AT boludasusana pathologicalchangesinducedbyalzheimersbraininoculationinamyloidbetaplaquebearingmice
AT petitfanny pathologicalchangesinducedbyalzheimersbraininoculationinamyloidbetaplaquebearingmice
AT eddarkaouisabiha pathologicalchangesinducedbyalzheimersbraininoculationinamyloidbetaplaquebearingmice
AT cambonkarine pathologicalchangesinducedbyalzheimersbraininoculationinamyloidbetaplaquebearingmice
AT pathologicalchangesinducedbyalzheimersbraininoculationinamyloidbetaplaquebearingmice
AT picqjeanluc pathologicalchangesinducedbyalzheimersbraininoculationinamyloidbetaplaquebearingmice
AT bueeluc pathologicalchangesinducedbyalzheimersbraininoculationinamyloidbetaplaquebearingmice
AT duyckaertscharles pathologicalchangesinducedbyalzheimersbraininoculationinamyloidbetaplaquebearingmice
AT haikstephane pathologicalchangesinducedbyalzheimersbraininoculationinamyloidbetaplaquebearingmice
AT dhenainmarc pathologicalchangesinducedbyalzheimersbraininoculationinamyloidbetaplaquebearingmice