Prostacyclin Promotes Degenerative Pathology in a Model of Alzheimer’s Disease

Tasha R. Womack, Craig T. Vollert, Odochi Ohia-Nwoko, Monika Schmitt, Saghi Montazari, Tina L. Beckett, David Mayerich, Michael Paul Murphy, Jason L. Eriksen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is the most common form of dementia in aged populations. A substantial amount of data demonstrates that chronic neuroinflammation can accelerate neurodegenerative pathologies. In AD, chronic neuroinflammation results in the upregulation of cyclooxygenase and increased production of prostaglandin H2, a precursor for many vasoactive prostanoids. While it is well-established that many prostaglandins can modulate the progression of neurodegenerative disorders, the role of prostacyclin (PGI2) in the brain is poorly understood. We have conducted studies to assess the effect of elevated prostacyclin biosynthesis in a mouse model of AD. Upregulated prostacyclin expression significantly worsened multiple measures associated with amyloid-β (Aβ) disease pathologies. Mice overexpressing both Aβ and PGI2 exhibited impaired learning and memory and increased anxiety-like behavior compared with non-transgenic and PGI2 control mice. PGI2 overexpression accelerated the development of Aβ accumulation in the brain and selectively increased the production of soluble Aβ42. PGI2 damaged the microvasculature through alterations in vascular length and branching; Aβ expression exacerbated these effects. Our findings demonstrate that chronic prostacyclin expression plays a novel and unexpected role that hastens the development of the AD phenotype.

Original languageEnglish
Article number769347
JournalFrontiers in Cellular Neuroscience
StatePublished - Feb 7 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 Womack, Vollert, Ohia-Nwoko, Schmitt, Montazari, Beckett, Mayerich, Murphy and Eriksen.


  • Alzheimer’s disease
  • amyloid-β
  • neurodegeneration
  • neuroinflammation
  • prostanoid

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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