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

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.

Automated summary

Preeclampsia (PE) is a major cause of maternal and fetal mortality worldwide, and may lead to dementia later in life. The etiological drivers of PE are still unknown. Cis P-tau is a potential biomarker and etiological driver in pre-clinical Alzheimer's and after brain injury, and can be targeted by a specific antibody. Research has found significant levels of cis P-tau in the placenta and serum of PE patients, indicating its potential role in the development of the disease. The depletion of cis P-tau by the antibody prevents the disruption of trophoblast invasion and endovascular activity, providing valuable insights for early diagnosis and treatment of PE.