Alzheimer's Disease: Exercise Therapy and Brain Networks (2021-2022)

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

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 focus on outreach by developing and populating a website to explain the project and share programs, data and analyses.

Learn more about this project team by viewing the team's video.

Anticipated Outputs

Final report/poster for science meeting; public presentation or website; methodology for analyzing imaging and data; apparatus for delivering odors to mice during imaging

Student Opportunities

Ideally, this project team will be comprised of 1-2 graduate students and 3-5 undergraduate students. Prospective team members will likely be from neuroscience, biology or biomedical engineering programs or majors. Students who are majoring in computer science, statistics or other types of engineering with either a background or interest in biological sciences are also encouraged to apply. Team leaders are looking for students with mathematical, engineering or computer science inclinations, some expertise in brain imaging technology and the ability to produce web-based presentations.

Students will learn about the biology of Alzheimer’s disease and the mechanisms through which exercise alters the body, brain and behavior. Computation, programming, and statistical and data management skills will be developed as students analyze and compare brain imaging data from mouse models of Alzheimer’s disease to brain neuropathology, behavioral data and databases of human brain imaging from Alzheimer’s patients.

Team members will contribute to publications and posters and present these to the research community and clinical consumers. Since this project uses a mouse model, students will learn about the ethics of animal research and its value to studying human disease and later translating the research into therapeutic interventions.

The team-based project in the NEUROSCI 278: Sex/Gender: Nature/Nurture course and the lab research experiences will all involve multiple students working together. Students will be encouraged to present new data, discuss roadblocks in data collection and analysis, and describe findings from relevant new research articles.

Janai Williams will serve as project manager.

Timing

Summer 2021 – Summer 2022

  • Summer 2021 (optional): Complete all needed online training and background checks to do animal research
  • Fall 2021: Start project components and weekly team meetings; take NEUROSCI 278: Sex/Gender: Nature/Nurture course (new team members); do a neuroscience practicum or independent study to learn basic methods and begin data collection (new team members); continue lab research as part of a senior thesis project (optional for continuing team members)
  • Spring 2022: 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 2022 (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

Crediting 

Academic credit available for fall and spring semesters; summer funding available

See earlier related team, Exercise Therapy and Brain Networks: Implications for Alzheimer's Disease (2020-2021).

Brain.

Team Leaders

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

/graduate Team Members

  • Janai Williams, Psychology-PHD

/yfaculty/staff Team Members

  • Carol Colton, School of Medicine-Neurology
  • Jacques Stout, School of Medicine-Brain Imaging and Analysis Center
  • Ara Wilson, Arts & Sciences-Gender, Sexuality, and Feminist Studies