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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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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 |
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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 |
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