Open AccessElevated 4R‐tau in astrocytes from asymptomatic carriers of the MAPT 10+16 intronic mutation
Author(s) -
SetóSalvia Núria,
Esteras Noemi,
Silva Rohan,
PabloFernandez 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.
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17136
Subject(s) - tau protein , biology , frontotemporal lobar degeneration , pathogenesis , gene isoform , mutation , asymptomatic carrier , microbiology and biotechnology , tauopathy , asymptomatic , gene , pathology , genetics , alzheimer's disease , frontotemporal dementia , neurodegeneration , medicine , immunology , dementia , disease
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.