Alzheimer's Disease: Exercise Therapy and Brain Networks (2022-2023)

Background

More than five million Americans are afflicted with Alzheimer’s disease. This number is expected to escalate, as the proportion of older Americans continues to rise. Age, apolipoprotein E (APOE-ε4) and chromosomal sex are well-established risk factors.

Because Alzheimer’s disease has 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 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 Alzheimer’s disease in well-controlled environments that can help facilitate development of early interventions. In vivo magnetic resonance imaging (MRI) can be used in both humans and mice to identify vulnerable circuits that may predict cognitive decline.

Project Description

Building on the work of the 2021-2022 team, this project team will examine brain structure and function in transgenic mice that develop symptoms of Alzheimer’s disease, evaluate whether menopause accelerates cognitive decline and neuropathogenesis and assess whether chronic exercise can mitigate this risk.

Team members will develop protocols and collect data to determine if functional MRI changes in the brain can be seen as Alzheimer’s disease progresses, by training mice to find one odor negative and aversive and a second odor positive and appetitive. Mice will then be anesthetized and presented with these odors plus a novel odor during MRI scanning. Once these procedures are verified and brain functional changes detected, the team can examine various models and their controls and determine the effect of exercise therapy and/or menopause. 

To answer these complex questions, team members will be involved in all aspects of the project from developing devices and research protocols, to piloting behavioral training procedures, to developing programs for data acquisition and analysis, to examining postmortem brain tissue. For example, the team will design animal support beds, test novel odor delivery instruments and seek to build simple MRI signal detection probes.
Team members will also develop a website to explain the project and share programs, data and analyses.

Anticipated Outputs

Reports and/or posters for science meetings, leading to eventual manuscript for peer-reviewed publication; public presentation; methodology for analyzing imaging and data; apparatus for delivering odors to mice during imaging

Timing

Summer 2022 – Summer 20223

  • Summer 2022 (optional): Complete all needed online training and background checks to do animal research
  • Fall 2022: Start project components and weekly team meetings; take optional course, Sex/Gender: Nature/Nurture (new team members); do neuroscience practicum or independent study to learn basic methods and begin data collection (new team members); continue lab research as part of senior thesis project (optional for continuing team members)
  • Spring 2023: Continue doing background reading, hands-on laboratory work; collect and analyze data; draft possible article for a journal; create shared website for presenting work to public; work on correlations and collaboration between component parts 
  • Summer 2023 (optional): Complete data collection and focus on analysis for 35 hours/week for 6-8 weeks; develop website and outreach presentation; develop protocols for follow-up projects

See earlier related team, Alzheimer's Disease: Exercise Therapy and Brain Networks (2021-2022).
 

Image: Brain Inflammation from Alzheimer's Disease, by National Institute on Aging, NIH, licensed under CC BY-NC 2.0

Alzheimer's.

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

  • Nikhil Gadiraju, Biomedical Engineering (BSE)
  • Jasmine King
  • Pradnesh Kolluru
  • Anna MacFarlane, Neuroscience (BS)
  • Isabella Pansini, Neuroscience (BS)
  • Divya Reddy, Biology (BS)
  • Celine Wang
  • Eileen Wen, Neuroscience (BS), Economics (BS2)

/yfaculty/staff Team Members

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