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2020 Alzheimer's Association Research Grant (AARG)

Do Lifestyles Induce Cell Plasticity? A Molecular Query Across Human Trials

How do positive lifestyle changes benefit the brain?

Kaitlin Casaletto, Ph.D.
University of California
San Francisco, CA - United States



Background

Researchers believe that there is not a single cause of Alzheimer’s, but rather it develops over time as a result of multiple factors such as lifestyle, environment, and genetics. Studies show that active lifestyle may impact the development of Alzheimer’s and other dementia but the biological mechanisms by which an activity may impact a person’s risk for Alzheimer’s is not known. 

Recently, scientists have developed a novel method that analyzes small, pouch-like structures called “exosomes”. Exosomes are released by cells in our body— including nerve cells in the brain— into tissue, bodily fluids including blood. The exosomes contain proteins and other genetic materials that provide instructions to make these proteins. Dr. Kaitlin Casaletto and colleagues will analyze proteins found in exosomes, following lifestyle changes. Dr. Casaletto believes that measuring these proteins in exosomes may serve as biological markers (biomarkers) of the underlying biology linking positive lifestyle changes to reduced risk for Alzheimer’s and other brain disorders.
 

Research Plan

The researchers will leverage two lifestyle intervention studies- the Mental Activity and eXercise (MAX) Trial and an ongoing Activities for Aging Neurogenesis (ActAN) Trial. These trials have introduced positive lifestyle interventions in older adults through cognitive stimulation or exercise. Using blood samples collected from participants of both the studies, Dr. Casaletto and colleagues will measure the different patterns of proteins found in the exosomes. Dr. Casaletto believes that after the lifestyle interventions (such as physical and cognitive activities), the exosomes may have higher levels of proteins that are associated with benefits for the brain cells and lower levels of proteins associated with brain inflammation and damage.

Furthermore, the researchers will study the changes in these biological markers and analyze whether they can be associated with cognitive changes in participants following lifestyle changes from both trials.
 

Impact

The study results may identify biomarkers in the brain that could change in response to cognitive stimulation and exercise. It may also give us new insights into the underlying biology linking lifestyle interventions and reduced risk for Alzheimer’s and other brain diseases.

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