Seto-Salvia, N;
Esteras, N;
de Silva, R;
de Pablo-Fernandez, E;
Arber, C;
Toomey, CE;
Polke, JM;
... Warner, TT; + view all
(2021)
Elevated 4R-tau in astrocytes from asymptomatic carriers of the MAPT 10+16 intronic mutation.
Journal of Cellular and Molecular Medicine
10.1111/jcmm.17136.
(In press).
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J Cellular Molecular Medi - 2021 - Set ‐Salvia - Elevated 4R‐tau in astrocytes from asymptomatic carriers of the MAPT 10 16.pdf - Published Version Download (560kB) | Preview |
Abstract
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.
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