Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau
The relationship between the two most prominent neuropathological hallmarks of Alzheimer’s Disease (AD), extracellular amyloid-β (Aβ) deposits and intracellular accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFT), remains at present not fully understood. A large body of evidence...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/10/5191 |
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| author | Silvia Zampar Oliver Wirths |
| author_facet | Silvia Zampar Oliver Wirths |
| author_sort | Silvia Zampar |
| collection | DOAJ |
| description | The relationship between the two most prominent neuropathological hallmarks of Alzheimer’s Disease (AD), extracellular amyloid-β (Aβ) deposits and intracellular accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFT), remains at present not fully understood. A large body of evidence places Aβ upstream in the cascade of pathological events, triggering NFTs formation and the subsequent neuron loss. Extracellular Aβ deposits were indeed causative of an increased tau phosphorylation and accumulation in several transgenic models but the contribution of soluble Aβ peptides is still controversial. Among the different Aβ variants, the N-terminally truncated peptide Aβ<sub>4–42</sub> is among the most abundant. To understand whether soluble Aβ<sub>4–42</sub> peptides impact the onset or extent of tau pathology, we have crossed the homozygous Tg4–42 mouse model of AD, exclusively expressing Aβ<sub>4–42</sub> peptides, with the PS19 (P301S) tau transgenic model. Behavioral assessment showed that the resulting double-transgenic line presented a partial worsening of motor performance and spatial memory deficits in the aged group. While an increased loss of distal CA1 pyramidal neurons was detected in young mice, no significant alterations in hippocampal tau phosphorylation were observed in immunohistochemical analyses. |
| first_indexed | 2024-03-10T11:25:16Z |
| format | Article |
| id | doaj.art-de83741fe43b4fdd8f8581cd7839257c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T11:25:16Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-de83741fe43b4fdd8f8581cd7839257c2023-11-21T19:44:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012210519110.3390/ijms22105191Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant TauSilvia Zampar0Oliver Wirths1Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, D-37075 Göttingen, GermanyDepartment of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, D-37075 Göttingen, GermanyThe relationship between the two most prominent neuropathological hallmarks of Alzheimer’s Disease (AD), extracellular amyloid-β (Aβ) deposits and intracellular accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFT), remains at present not fully understood. A large body of evidence places Aβ upstream in the cascade of pathological events, triggering NFTs formation and the subsequent neuron loss. Extracellular Aβ deposits were indeed causative of an increased tau phosphorylation and accumulation in several transgenic models but the contribution of soluble Aβ peptides is still controversial. Among the different Aβ variants, the N-terminally truncated peptide Aβ<sub>4–42</sub> is among the most abundant. To understand whether soluble Aβ<sub>4–42</sub> peptides impact the onset or extent of tau pathology, we have crossed the homozygous Tg4–42 mouse model of AD, exclusively expressing Aβ<sub>4–42</sub> peptides, with the PS19 (P301S) tau transgenic model. Behavioral assessment showed that the resulting double-transgenic line presented a partial worsening of motor performance and spatial memory deficits in the aged group. While an increased loss of distal CA1 pyramidal neurons was detected in young mice, no significant alterations in hippocampal tau phosphorylation were observed in immunohistochemical analyses.https://www.mdpi.com/1422-0067/22/10/5191Alzheimer’ diseaseamyloid βtaubehaviorneuron losstransgenic mice |
| spellingShingle | Silvia Zampar Oliver Wirths Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau International Journal of Molecular Sciences Alzheimer’ disease amyloid β tau behavior neuron loss transgenic mice |
| title | Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau |
| title_full | Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau |
| title_fullStr | Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau |
| title_full_unstemmed | Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau |
| title_short | Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau |
| title_sort | characterization of a mouse model of alzheimer s disease expressing aβ4 42 and human mutant tau |
| topic | Alzheimer’ disease amyloid β tau behavior neuron loss transgenic mice |
| url | https://www.mdpi.com/1422-0067/22/10/5191 |
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