Alzheimer's disease-like neuropathology of gene-targeted APP-SLxPS1mut mice expressing the amyloid precursor protein at endogenous levels
Most transgenic mice used for preclinical evaluation of potential disease-modifying treatments of Alzheimer's disease develop major histopathological features of this disease by several-fold overexpression of the human amyloid precursor protein. We studied the phenotype of three different strai...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2005-11-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996105001257 |
| _version_ | 1818573112760860672 |
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| author | Christoph Köhler Ulrich Ebert Karlheinz Baumann Hannsjörg Schröder |
| author_facet | Christoph Köhler Ulrich Ebert Karlheinz Baumann Hannsjörg Schröder |
| author_sort | Christoph Köhler |
| collection | DOAJ |
| description | Most transgenic mice used for preclinical evaluation of potential disease-modifying treatments of Alzheimer's disease develop major histopathological features of this disease by several-fold overexpression of the human amyloid precursor protein. We studied the phenotype of three different strains of gene-targeted mice which express the amyloid precursor protein at endogenous levels. Only further crossing with transgenic mice overexpressing mutant human presenilin1 led to the deposition of extracellular amyloid, accompanied by the deposition of apolipoprotein E, an astrocyte and microglia reaction, and the occurrence of dilated cholinergic terminals in the cortex. Features of neurodegeneration, however, were absent. The pattern of plaque development and deposition in these mice was similar to that of amyloid precursor protein overproducing strains if crossed to presenilin1-transgenics. However, plaque development started much later and developed slowly until the age of 18 months but then increased more rapidly. |
| first_indexed | 2024-12-15T00:06:44Z |
| format | Article |
| id | doaj.art-864eb377dcd34dce819a1726c992b05d |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-15T00:06:44Z |
| publishDate | 2005-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-864eb377dcd34dce819a1726c992b05d2022-12-21T22:42:42ZengElsevierNeurobiology of Disease1095-953X2005-11-01202528540Alzheimer's disease-like neuropathology of gene-targeted APP-SLxPS1mut mice expressing the amyloid precursor protein at endogenous levelsChristoph Köhler0Ulrich Ebert1Karlheinz Baumann2Hannsjörg Schröder3Institute II of Anatomy, Department of Neuroanatomy, University of Cologne, Josef Stelzmann-Straße 9, D-50931 Cologne, Germany; Corresponding author. Fax: +49 221 478 3836.Pharma Research CNS, Bayer Health Care AG, D-42096 Wuppertal, GermanyPharma Research CNS, Bayer Health Care AG, D-42096 Wuppertal, GermanyInstitute II of Anatomy, Department of Neuroanatomy, University of Cologne, Josef Stelzmann-Straße 9, D-50931 Cologne, GermanyMost transgenic mice used for preclinical evaluation of potential disease-modifying treatments of Alzheimer's disease develop major histopathological features of this disease by several-fold overexpression of the human amyloid precursor protein. We studied the phenotype of three different strains of gene-targeted mice which express the amyloid precursor protein at endogenous levels. Only further crossing with transgenic mice overexpressing mutant human presenilin1 led to the deposition of extracellular amyloid, accompanied by the deposition of apolipoprotein E, an astrocyte and microglia reaction, and the occurrence of dilated cholinergic terminals in the cortex. Features of neurodegeneration, however, were absent. The pattern of plaque development and deposition in these mice was similar to that of amyloid precursor protein overproducing strains if crossed to presenilin1-transgenics. However, plaque development started much later and developed slowly until the age of 18 months but then increased more rapidly.http://www.sciencedirect.com/science/article/pii/S0969996105001257Amyloid precursor proteinGene-targetedAmyloid depositsMicrogliaCholine acetyltransferaseApolipoprotein E |
| spellingShingle | Christoph Köhler Ulrich Ebert Karlheinz Baumann Hannsjörg Schröder Alzheimer's disease-like neuropathology of gene-targeted APP-SLxPS1mut mice expressing the amyloid precursor protein at endogenous levels Neurobiology of Disease Amyloid precursor protein Gene-targeted Amyloid deposits Microglia Choline acetyltransferase Apolipoprotein E |
| title | Alzheimer's disease-like neuropathology of gene-targeted APP-SLxPS1mut mice expressing the amyloid precursor protein at endogenous levels |
| title_full | Alzheimer's disease-like neuropathology of gene-targeted APP-SLxPS1mut mice expressing the amyloid precursor protein at endogenous levels |
| title_fullStr | Alzheimer's disease-like neuropathology of gene-targeted APP-SLxPS1mut mice expressing the amyloid precursor protein at endogenous levels |
| title_full_unstemmed | Alzheimer's disease-like neuropathology of gene-targeted APP-SLxPS1mut mice expressing the amyloid precursor protein at endogenous levels |
| title_short | Alzheimer's disease-like neuropathology of gene-targeted APP-SLxPS1mut mice expressing the amyloid precursor protein at endogenous levels |
| title_sort | alzheimer s disease like neuropathology of gene targeted app slxps1mut mice expressing the amyloid precursor protein at endogenous levels |
| topic | Amyloid precursor protein Gene-targeted Amyloid deposits Microglia Choline acetyltransferase Apolipoprotein E |
| url | http://www.sciencedirect.com/science/article/pii/S0969996105001257 |
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