Alzheimer disease models and human neuropathology: similarities and differences.
International audience Animal models aim to replicate the symptoms, the lesions or the cause(s) of Alzheimer disease. Numerous mouse transgenic lines have now succeeded in partially reproducing its lesions: the extracellular deposits of Abeta peptide and the intracellular accumulation of tau protein...
Published in: | Acta Neuropathologica |
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Main Authors: | , , |
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Format: | Article in Journal/Newspaper |
Language: | English |
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HAL CCSD
2008
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Online Access: | https://hal.archives-ouvertes.fr/hal-00320572 https://hal.archives-ouvertes.fr/hal-00320572/document https://hal.archives-ouvertes.fr/hal-00320572/file/2008BDelatour_Alzheimer%20disease%20models.pdf https://doi.org/10.1007/s00401-007-0312-8 |
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Université de Nantes: HAL-UNIV-NANTES |
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English |
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[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology |
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[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Duyckaerts, Charles Potier, Marie-Claude Delatour, Benoit Alzheimer disease models and human neuropathology: similarities and differences. |
topic_facet |
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology |
description |
International audience Animal models aim to replicate the symptoms, the lesions or the cause(s) of Alzheimer disease. Numerous mouse transgenic lines have now succeeded in partially reproducing its lesions: the extracellular deposits of Abeta peptide and the intracellular accumulation of tau protein. Mutated human APP transgenes result in the deposition of Abeta peptide, similar but not identical to the Abeta peptide of human senile plaque. Amyloid angiopathy is common. Besides the deposition of Abeta, axon dystrophy and alteration of dendrites have been observed. All of the mutations cause an increase in Abeta 42 levels, except for the Arctic mutation, which alters the Abeta sequence itself. Overexpressing wild-type APP alone (as in the murine models of human trisomy 21) causes no Abeta deposition in most mouse lines. Doubly (APP x mutated PS1) transgenic mice develop the lesions earlier. Transgenic mice in which BACE1 has been knocked out or overexpressed have been produced, as well as lines with altered expression of neprilysin, the main degrading enzyme of Abeta. The APP transgenic mice have raised new questions concerning the mechanisms of neuronal loss, the accumulation of Abeta in the cell body of the neurons, inflammation and gliosis, and the dendritic alterations. They have allowed some insight to be gained into the kinetics of the changes. The connection between the symptoms, the lesions and the increase in Abeta oligomers has been found to be difficult to unravel. Neurofibrillary tangles are only found in mouse lines that overexpress mutated tau or human tau on a murine tau -/- background. A triply transgenic model (mutated APP, PS1 and tau) recapitulates the alterations seen in AD but its physiological relevance may be discussed. A number of modulators of Abeta or of tau accumulation have been tested. A transgenic model may be analyzed at three levels at least (symptoms, lesions, cause of the disease), and a reading key is proposed to summarize this analysis. |
author2 |
Laboratoire de Neuropathologie Raymond Escourolle CHU Pitié-Salpétriêre Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière AP-HP Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) Neurobiologie et diversité cellulaire (NDC) Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris) Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS) Neurobiologie de l'apprentissage, de la mémoire et de la communication (NAMC) Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS) |
format |
Article in Journal/Newspaper |
author |
Duyckaerts, Charles Potier, Marie-Claude Delatour, Benoit |
author_facet |
Duyckaerts, Charles Potier, Marie-Claude Delatour, Benoit |
author_sort |
Duyckaerts, Charles |
title |
Alzheimer disease models and human neuropathology: similarities and differences. |
title_short |
Alzheimer disease models and human neuropathology: similarities and differences. |
title_full |
Alzheimer disease models and human neuropathology: similarities and differences. |
title_fullStr |
Alzheimer disease models and human neuropathology: similarities and differences. |
title_full_unstemmed |
Alzheimer disease models and human neuropathology: similarities and differences. |
title_sort |
alzheimer disease models and human neuropathology: similarities and differences. |
publisher |
HAL CCSD |
publishDate |
2008 |
url |
https://hal.archives-ouvertes.fr/hal-00320572 https://hal.archives-ouvertes.fr/hal-00320572/document https://hal.archives-ouvertes.fr/hal-00320572/file/2008BDelatour_Alzheimer%20disease%20models.pdf https://doi.org/10.1007/s00401-007-0312-8 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Acta Neuropathol https://hal.archives-ouvertes.fr/hal-00320572 Acta Neuropathol, 2008, 115 (1), pp.5-38. ⟨10.1007/s00401-007-0312-8⟩ |
op_relation |
info:eu-repo/semantics/altIdentifier/doi/10.1007/s00401-007-0312-8 info:eu-repo/semantics/altIdentifier/pmid/18038275 hal-00320572 https://hal.archives-ouvertes.fr/hal-00320572 https://hal.archives-ouvertes.fr/hal-00320572/document https://hal.archives-ouvertes.fr/hal-00320572/file/2008BDelatour_Alzheimer%20disease%20models.pdf doi:10.1007/s00401-007-0312-8 PUBMED: 18038275 PUBMEDCENTRAL: PMC2100431 |
op_rights |
info:eu-repo/semantics/OpenAccess |
op_doi |
https://doi.org/10.1007/s00401-007-0312-8 |
container_title |
Acta Neuropathologica |
container_volume |
115 |
container_issue |
1 |
container_start_page |
5 |
op_container_end_page |
38 |
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1766346385945264128 |
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ftunivnantes:oai:HAL:hal-00320572v1 2023-05-15T15:16:04+02:00 Alzheimer disease models and human neuropathology: similarities and differences. Duyckaerts, Charles Potier, Marie-Claude Delatour, Benoit Laboratoire de Neuropathologie Raymond Escourolle CHU Pitié-Salpétriêre Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière AP-HP Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) Neurobiologie et diversité cellulaire (NDC) Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris) Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS) Neurobiologie de l'apprentissage, de la mémoire et de la communication (NAMC) Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS) 2008-01-05 https://hal.archives-ouvertes.fr/hal-00320572 https://hal.archives-ouvertes.fr/hal-00320572/document https://hal.archives-ouvertes.fr/hal-00320572/file/2008BDelatour_Alzheimer%20disease%20models.pdf https://doi.org/10.1007/s00401-007-0312-8 en eng HAL CCSD info:eu-repo/semantics/altIdentifier/doi/10.1007/s00401-007-0312-8 info:eu-repo/semantics/altIdentifier/pmid/18038275 hal-00320572 https://hal.archives-ouvertes.fr/hal-00320572 https://hal.archives-ouvertes.fr/hal-00320572/document https://hal.archives-ouvertes.fr/hal-00320572/file/2008BDelatour_Alzheimer%20disease%20models.pdf doi:10.1007/s00401-007-0312-8 PUBMED: 18038275 PUBMEDCENTRAL: PMC2100431 info:eu-repo/semantics/OpenAccess Acta Neuropathol https://hal.archives-ouvertes.fr/hal-00320572 Acta Neuropathol, 2008, 115 (1), pp.5-38. ⟨10.1007/s00401-007-0312-8⟩ [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology info:eu-repo/semantics/article Journal articles 2008 ftunivnantes https://doi.org/10.1007/s00401-007-0312-8 2022-10-18T23:31:50Z International audience Animal models aim to replicate the symptoms, the lesions or the cause(s) of Alzheimer disease. Numerous mouse transgenic lines have now succeeded in partially reproducing its lesions: the extracellular deposits of Abeta peptide and the intracellular accumulation of tau protein. Mutated human APP transgenes result in the deposition of Abeta peptide, similar but not identical to the Abeta peptide of human senile plaque. Amyloid angiopathy is common. Besides the deposition of Abeta, axon dystrophy and alteration of dendrites have been observed. All of the mutations cause an increase in Abeta 42 levels, except for the Arctic mutation, which alters the Abeta sequence itself. Overexpressing wild-type APP alone (as in the murine models of human trisomy 21) causes no Abeta deposition in most mouse lines. Doubly (APP x mutated PS1) transgenic mice develop the lesions earlier. Transgenic mice in which BACE1 has been knocked out or overexpressed have been produced, as well as lines with altered expression of neprilysin, the main degrading enzyme of Abeta. The APP transgenic mice have raised new questions concerning the mechanisms of neuronal loss, the accumulation of Abeta in the cell body of the neurons, inflammation and gliosis, and the dendritic alterations. They have allowed some insight to be gained into the kinetics of the changes. The connection between the symptoms, the lesions and the increase in Abeta oligomers has been found to be difficult to unravel. Neurofibrillary tangles are only found in mouse lines that overexpress mutated tau or human tau on a murine tau -/- background. A triply transgenic model (mutated APP, PS1 and tau) recapitulates the alterations seen in AD but its physiological relevance may be discussed. A number of modulators of Abeta or of tau accumulation have been tested. A transgenic model may be analyzed at three levels at least (symptoms, lesions, cause of the disease), and a reading key is proposed to summarize this analysis. Article in Journal/Newspaper Arctic Université de Nantes: HAL-UNIV-NANTES Arctic Acta Neuropathologica 115 1 5 38 |