Angiogenic and anti-angiogenic factors are the shared mechanistic pathways between preeclampsia and Alzheimer's disease: Perspective and take-away.

Preeclampsia (PE), a major hypertensive disorder of pregnancy, is increasingly recognized as a significant risk factor for cognitive decline and Alzheimer's disease (AD). Placental ischemia in PE leads to an anti-angiogenic state, characterized by elevated soluble FMS-like tyrosine kinase-1 (sFlt-1) and reduced placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), causing systemic endothelial dysfunction. These alterations may persist during the postpartum period, promoting cerebrovascular impairment, blood-brain barrier (BBB) disruption, and neuroinflammation. Furthermore, PE is associated with the release of AD-related proteins, including amyloid-beta (Aβ) and hyperphosphorylated tau protein. However, the potential link between AD and PE regarding the angiogenic and anti-angiogenic factors is not fully elucidated. This review aims to explore the shared pathophysiological pathways, focusing on the angiogenic and anti-angiogenic factors. The manuscript also evaluates the potential for repurposing pharmacological agents to mitigate the long-term risk of AD in women with a history of PE.