Exercise reduces Alzheimer’s risk. Why?

RESEARCH INDICATES that exercise can reduce the risk of Alzheimer’s disease. The problem, however, is that we don’t know why.

By understanding the precise processes happening in the body when we exercise, Bruce Lamb, PhD, who holds the Roberts Family Chair in Alzheimer’s Disease Research, hopes to replicate the mechanisms with new drugs or therapies.

Specifically, Lamb will study what role exercise may play in reducing inflammation and how this is linked to Alzheimer’s disease. By understanding the precise processes happening in the body when we exercise, researchers could then seek to replicate the mechanisms with new drugs or therapies.

In other words, scientists could develop medications that produce the same benefit as taking a run on the treadmill or hitting the elliptical machine. (Lamb is quick to point out that even if we reach that milestone, he sees any such therapy as a supplement—not a replacement—for actual exercise.)

“Understanding the potential benefits of lifestyle interventions such as exercise and diet is critically important, but that alone is not enough,” said Lamb, who holds the Roberts Family Chair in Alzheimer’s Disease Research. “We also must understand exactly how these interventions help protect us from Alzheimer’s disease. Only then can we exploit our body’s natural defense mechanisms to develop therapeutics that will help everyone, regardless of physical limitations or age.

Lamb’s pre-clinical research will engage a unique type of athlete: transgenic mice that have been altered to have a predisposition for Alzheimer’s disease. The mice will run on a wheel in the laboratory, allowing Lamb’s team to monitor and study changes happening at a cellular level.

He will partner with a former colleague at Cleveland Clinic who is conducting a complementary clinical trial in patients. IU School of Medicine and Cleveland Clinic are jointly receiving $8.75 million to conduct the clinical and laboratory studies.

The work dovetails with Lamb’s other major new initiative: developing mouse models for Alzheimer’s disease that more closely mimic the condition in humans. Too often, drugs that appeared promising in laboratory studies fail when they reach clinical trials in people. One theory is that the mice used in the studies don’t reflect what the disease truly looks like in people.

The National Institute on Aging has awarded Lamb a $25 million grant to develop models that are more accurate, thereby accelerating the pace of drug development.

“I am excited to be working on this research and excited about the potential it holds for patients,” Lamb said.