Exercise Therapy and Brain Networks: Implications for Alzheimer's Disease (2020-2021)

Background

An estimated 5.3 million Americans are afflicted with Alzheimer’s disease (AD). This number is expected to escalate, as the proportion of older Americans continues to rise.

Because AD is a multifactorial disease with both genetic and environmental causes, considerable research has focused on environmental factors including lifestyle and nutrition as potential therapeutic interventions that might delay or prevent AD neuropathology and cognitive decline. Recent advances have provided clinical evidence for the efficacy of exercise in preserving brain function in aging humans. Mouse models provide opportunities to study characteristics of AD in well-controlled environments that can help facilitate development of early interventions. In vivo MRI can be used in both humans and mice to identify vulnerable circuits that may predict cognitive decline.

Project Description

The project’s overarching goal is to examine brain structure and function in transgenic mice with human APOE- ε4 that develop symptoms of AD and compare those with mice with human APOE-ε3 that are not at risk. The team will also evaluate whether menopause accelerates cognitive decline and neuropathogenesis in AD and whether chronic exercise can mitigate this risk.

The 2020-2021 team will build on previous teams’ method for inducing ovarian failure in mice without removing the ovary. Team members will move from a mouse model of familiar AD to a model of sporadic AD; examine morphometric changes in brain regional volumes and connectivity using in vivo MRI methods; and use new methods for examining olfactory memory that can be used during in vivo MRIs, which are routinely used to diagnose and follow AD progression in humans.

The team will also compare the mouse brain MRI data with online databases of human brain changes during AD progression. Tracking and comparing changes in brain structure with disease progression and correlating these changes with pathological indicators will allow team members to test the validity of the mouse models – a critical step in mouse modeling of a human brain disease where cross comparison is needed to translate findings to human disease.

Anticipated Outputs

Final report/poster for science meeting; public presentation or website; methodology for analyzing imaging and data

Timing

Fall 2020 – Summer 2021

  • Fall 2020: Take Sex/Gender: Nature/Nurture course; participate in weekly team meetings; learn basic methods; begin data collection
  • Spring 2021: Do background reading and hands-on laboratory work; collect and analyze data
  • Summer 2021 (optional): Complete data collection; focus on analysis; develop website; develop and present outreach presentation

See earlier related team, Exercise Therapy and Brain Networks: Implications for Alzheimer’s Disease (2019-2020).

Jump rope.

Team Leaders

  • Alexandra Badea, School of Medicine-Radiology
  • Christina L. Williams, Arts & Sciences-Psychology and Neuroscience

/graduate Team Members

  • Janai Williams, Psychology-PHD

/undergraduate Team Members

  • /undergraduate
  • Abinaya Lakshmanan, Biomedical Engineering (BSE), Computer Science (AB2)
  • Anna MacFarlane

/yfaculty/staff Team Members

  • Carol Colton, School of Medicine-Neurology
  • Ara Wilson, Arts & Sciences-Gender, Sexuality, and Feminist Studies