Discovery of biomarker for life-threatening pregnancy condition could inform diagnosis and treatments.
A protein in cerebrospinal fluid associated with Alzheimer’s disease is also a driver of the pregnancy condition of preeclampsia, and it can influence diagnosis and treatment of the condition.
Research led by Surendra Sharma, MD, PhD, and Sukanta Jash, PhD, at Brown University and Kun Ping Lu, MD, PhD, and Xia Zhen Zhou, MD, at Western University in Canada has identified the protein, cis P-tau, in the blood and placentas of people with preeclampsia. They also found that depleting cis P-tau prevented the development of preeclampsia in mice.
The researchers detailed their findings in Nature Communications.
“Our study identifies cis P-tau as a culprit and biomarker for preeclampsia,” says Sharma, a former Brown professor of pathology and laboratory medicine and of pediatrics (research) now at the University of Texas Medical Branch in Galveston. “It can be used for early diagnosis of the complication and is a crucial therapeutic target.”
Preeclampsia affects 5 percent to 8 percent of pregnancies globally and is the leading cause of maternal and fetal mortality due to premature delivery, complications with the placenta, and lack of oxygen. The root cause of preeclampsia has so far remained unknown, Sharma says, and without a known cause there has been no cure.
The protein cis P-tau has mainly been associated with neurological disorders like Alzheimer’s disease, traumatic brain injuries, and stroke. This association was discovered by Lu and Zhou in 2015 as a result of their decades of research on the role of tau protein in cancer and Alzheimer’s.
In 2016, Sharma and his team identified that preeclampsia and diseases like Alzheimer’s had similar root causes related to protein issues.
Sharma and Jash first met Lu and Zhou in 2019 at Brown, where Lu had been invited to discuss his research. Zhou had developed an antibody to target only the toxic cis P-tau protein while leaving its healthy counterpart unscathed. (The antibody has shown promising results in animal models and human cell cultures in treating the brain conditions, and is currently being tested in clinical trials in human patients with traumatic brain injury and Alzheimer’s.)
The Brown scientists had previously discovered that cis P-tau was significantly disregulated in the human placenta, comparable to what happens in the brains of people affected by Alzheimer’s.
The researchers became curious whether Zhou’s antibody could work as a potential treatment for preeclampsia.
In the new study, the researchers used multiple approaches to demonstrate the significance of tau in early- and late-onset preeclampsia, including measuring for cis P-tau in the blood and placenta from human patients with preeclampsia as well as depleting cis P-tau from a humanized mouse model of preeclampsia.
When the Brown researchers tested Zhou’s antibody in mouse models with preeclampsia, they discovered that the antibody depleted not only the cis P-tau protein but also some of the effects associated with preeclampsia.
“In this study, we found the cis P-tau antibody efficiently depleted the toxic protein in the blood and placenta, and corrected all features associated with preeclampsia in mice,” Sharma says. “Clinical features of preeclampsia, like elevated blood pressure, excessive protein in urine, and fetal growth restriction, among others, were eliminated and pregnancy was normal.”