Cis P-tau is a central circulating and placental etiologic driver and therapeutic target of preeclampsia

Sukanta Jash, Sayani Banerjee, Shibin Cheng, Bin Wang, Chenxi Qiu, Asami Kondo, Jan Ernerudh, Xiao Zhen Zhou (), Kun Ping Lu () and Surendra Sharma ()
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Sukanta Jash: Brown University
Sayani Banerjee: Brown University
Shibin Cheng: Brown University
Bin Wang: Harvard Medical School
Chenxi Qiu: Harvard Medical School
Asami Kondo: Harvard Medical School
Jan Ernerudh: Linköping University
Xiao Zhen Zhou: Western University
Kun Ping Lu: Western University
Surendra Sharma: Brown University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Preeclampsia (PE) is the leading cause of maternal and fetal mortality globally and may trigger dementia later in life in mothers and their offspring. However, the etiological drivers remain elusive. Cis P-tau is an early etiological driver and blood biomarker in pre-clinical Alzheimer’s and after vascular or traumatic brain injury, which can be targeted by stereo-specific antibody, with clinical trials ongoing. Here we find significant cis P-tau in the placenta and serum of PE patients, and in primary human trophoblasts exposed to hypoxia or sera from PE patients due to Pin1 inactivation. Depletion of cis P-tau from PE patient sera by the antibody prevents their ability to disrupt trophoblast invasion and endovascular activity and to cause the PE-like pathological and clinical features in pregnant humanized tau mice. Our studies uncover that cis P-tau is a central circulating etiological driver and its stereo-specific antibody is valuable for early PE diagnosis and treatment.

Date: 2023
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DOI: 10.1038/s41467-023-41144-6

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