Huang, M;
Macdonald, J;
Lavenir, I;
Chen, R;
Craxton, M;
Slavik-Smith, E;
Davies, SW;
(2022)
Increase in Tau Pathology in P290S Mapt Knock-In Mice Crossed with AppNL-G-F Mice.
eNeuro
, 9
(6)
, Article ENEURO.0247-22.2022. 10.1523/ENEURO.0247-22.2022.
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Abstract
Alzheimer's Disease (AD) is characterized by the pathological assembly of Aβ peptide, which deposits into extracellular plaques, and tau, which accumulates in intraneuronal inclusions. To investigate the link between Aβ and tau pathologies, experimental models featuring both pathologies are needed. We developed a mouse model featuring both tau and Aβ pathologies by knocking the P290S mutation into murine Mapt and crossing these MaptP290S KI mice with the AppNL-G-F KI line. MaptP290S KI mice developed a small number of tau inclusions, which increased with age. The amount of tau pathology was significantly larger in AppNL-G-FxMaptP290S KI mice from 18-months of age onwards. Tau pathology was higher in limbic areas, including hippocampus, amygdala and piriform/entorhinal cortex. We also observed AT100-and Gallyas-Braak-silver-positive dystrophic neurites containing assembled filamentous tau, as visualized by in situ EM. Using a cell-based tau seeding assay, we showed that sarkosyl-insoluble brain extracts from both 18-month-old MaptP290S KI and AppNL-G-FxMaptP290S KI mice were seed-competent, with brain extracts from double KI mice seeding significantly more than those from the MaptP290S KI mice. Finally, we showed that AppNL-G-FxMaptP290S KI mice had neurodegeneration in the piriform cortex from 18-months of age. We suggest that AppNL-G-F x MaptP290S KI mice provide a good model for studying the interactions of aggregation-prone tau, Aβ, neuritic plaques, neurodegeneration and aging.
| Type: | Article |
|---|---|
| Title: | Increase in Tau Pathology in P290S Mapt Knock-In Mice Crossed with AppNL-G-F Mice |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1523/ENEURO.0247-22.2022 |
| Publisher version: | https://doi.org/10.1523/ENEURO.0247-22.2022 |
| Language: | English |
| Additional information: | Copyright © 2022 Huang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
| Keywords: | Alzheimer’s disease, amyloid-β, knock-in, mouse model, tau |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10162995 |
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