| Autor: |
Set��-Salvia, N��ria, Esteras, Noemi, de Silva, Rohan, de Pablo-Fernandez, Eduardo, Arber, Charles, Toomey, Christina E, Polke, James M, Morris, Huw R, Rohrer, Jonathan D, Abramov, Andrey Y, Patani, Rickie, Wray, Selina, Warner, Thomas T |
| Rok vydání: |
2022 |
| Předmět: |
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| DOI: |
10.25418/crick.19188584.v1 |
| Popis: |
The microtubule-associated protein tau gene (MAPT) 10+16 intronic mutation causes frontotemporal lobar degeneration (FTLD) by increasing expression of four-repeat (4R)-tau isoforms. We investigated the potential role for astrocytes in the pathogenesis of FTLD by studying the expression of 4R-tau. We derived astrocytes and neurons from induced pluripotent stem cells from two asymptomatic 10+16 carriers which, compared to controls, showed persistently increased 4R:3R-tau transcript and protein ratios in both cell types. However, beyond 300 days culture, 10+16 neurons showed less marked increase of this 4R:3R-tau transcript ratio compared to astrocytes. Interestingly, throughout maturation, both 10+16 carriers consistently displayed different 4R:3R-tau transcript and protein ratios. These elevated levels of 4R-tau in astrocytes implicate glial cells in the pathogenic process and also suggests a cell-type-specific regulation and may inform and help on treatment of pre-clinical tauopathies. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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