# Amyloid-β fibrils accumulated in preeclamptic placentas suppress cytotrophoblast syncytialization

## TL;DR

This study shows that amyloid-β fibrils in preeclamptic placentas prevent cells from fusing, which is important for a healthy pregnancy.

## Contribution

The study reveals a new role for amyloid-β fibrils in the development of preeclampsia by inhibiting cytotrophoblast syncytialization.

## Key findings

- Amyloid-β levels and BACE-1 increase in preeclamptic placentas under hypoxia.
- Amyloid-β fibrils inhibit cytotrophoblast syncytialization by disrupting cell adhesion.
- Findings were confirmed using both cell models and primary human cytotrophoblasts.

## Abstract

Cerebral deposition of fibrillar amyloid-β is a pathological hallmark of Alzheimer’s disease. Cytotrophoblasts in the placenta produce amyloid β. Amyloid β deposits in preeclamptic placentas, and amyloid β fibrils can detrimentally suppress the syncytialization of cytotrophoblasts.

Cerebral deposition of fibrillar amyloid-β (Aβ) is a pathological hallmark of Alzheimer’s disease. Although Aβ is present in human placentas and accumulates in preeclamptic placentas characterized by poor placentation, the production and role of Aβ in the human placenta remain unclear. Because hypoxia in mid-to-late pregnancy is a risk for preeclampsia, we found that levels of hypoxia-inducible factor 1-α and β-secretase (BACE-1) increased concurrently with placental Aβ deposition in late-stage preeclamptic placentas. We also found that a human cytotrophoblast (CTB) model, BeWo cells, actually produced Aβ species and that hypoxia increased Aβ production and BACE-1 protein levels. Aβ42 fibrils inhibited CTB syncytialization, a critical step in maintaining pregnancy, by inducing loss of membrane localization of cell–cell adhesion molecules. Primary human CTBs confirmed these observations. Taken together, our results suggest that increased Aβ production in CTBs by hypoxia may lead to the formation of Aβ fibrils, which inhibit syncytiotrophoblast formation and are detrimental to pregnancy. Thus, our results reveal the novel role of Aβ fibrils in the pathogenesis of preeclampsia.