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Basic Science and Pathogenesis.

Caroline E Baggeroer1,2, Peter A Pietri3, Fiona E Harrison1,2,3,4

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Large arterial stiffness impairs spatial learning in male mice and memory in female Alzheimer

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Area of Science:

  • Neuroscience
  • Cardiovascular Science
  • Aging Research

Background:

  • Large arterial stiffness is linked to tau phosphorylation and neurodegeneration in humans.
  • Arterial stiffness often co-occurs with hypertension, atherosclerosis, and diabetes, complicating mechanistic studies.
  • Investigating large arterial stiffness's specific impact on brain function and Alzheimer's disease (AD) pathology is crucial.

Purpose of the Study:

  • To investigate the impact of surgically induced large artery stiffness on cognition.
  • To utilize a mouse model combining large artery stiffness with a transgenic model of tau pathology.

Main Methods:

  • Bilateral carotid calcification surgery using CaCl2 in P301S and wild-type mice.
  • Measurement of carotid compliance using Doppler ultrasound before and after surgery.
  • Behavioral testing including Morris Water Maze and Novel Object Recognition three weeks post-surgery.

Main Results:

  • CaCl2 exposure significantly decreased carotid artery compliance in treated mice.
  • Wildtype male mice showed impaired spatial learning in the Morris Water Maze.
  • Female P301S mice exhibited reduced long-term memory and potentially impaired working memory.

Conclusions:

  • Bilateral carotid calcification impairs spatial learning in male mice and memory in female P301S mice.
  • The carotid calcification model provides a tool to study the acceleration of tau pathology.
  • Further research will explore the link between carotid calcification and tau pathology progression.