Exercise Protects Against Alzheimer’s, And Scientists May Finally Know Why : ScienceAlert

Among its numerous health benefits, physical activity reduces the risk of developing Alzheimer’s disease. A new study on mice now dives into the specific mechanisms and proteins that allow exercise to protect our brains.

Scientists had previously determined that physical activity increases a protein called glycosylphosphatidylinositol-specific phospholipase D1 in the blood of mice, and that this protein is associated with good brain health.

That protein – more succinctly referred to as GPLD1 – strengthens the barrier that guards the brain against all sorts of unwelcome visitors within our blood, protecting against inflammation and subsequent cognitive decline.

A recent study led by a team from the University of California, San Francisco (UCSF), has identified a connection between GPLD1 and TNAP (tissue-nonspecific alkaline phosphatase) – an enzyme that typically ensures the barrier remains permeable when conditions get stressful.

Over time, however, TNAP accumulates within the blood-brain barrier’s cells, impairing their functionality. The study found GPLD1 ‘prunes’ TNAP from tissue, strengthening the brain’s protection against inflammation.

“This discovery shows just how relevant the body is for understanding how the brain declines with age,” says neuroscientist Saul Villeda, from UCSF.

Young mice that were genetically engineered to have more TNAP in their blood-brain barrier showed cognitive decline consistent with older mice.

When older mice were genetically engineered to have less TNAP than normal, leaks were reduced in the blood-brain barrier, inflammation went down, and cognitive abilities improved.

In mice with a model of Alzheimer’s disease, increased levels of GPLD1 or reduced levels of TNAP were both associated with fewer harmful clumps of the amyloid beta protein that are hallmarks of Alzheimer’s, another positive sign.

It’s well established that inflammation or neuron stress is a key player in Alzheimer’s and other aspects of brain aging and cognitive decline, and the blood-brain barrier protects against chemicals that could trigger that inflammation.

Thanks to the results of this investigation, it’s now clear that exercise produces GPLD1, GPLD1 keeps TNAP in check, and that means a stronger blood-brain barrier – and a lower risk of cognitive decline and conditions such as Alzheimer’s.

Knowing this opens the way to treatments that may mimic the positive actions of GPLD1 synthetically.

“We were able to tap into this mechanism late in life for the mice, and it still worked,” says neuroscientist Gregor Bieri, from UCSF.

That this research was only carried out in mice is a limitation of the study, but similar processes are likely happening in humans – something future research can look into.

Studies like this are doubly beneficial, in that they identify how specific health problems get started, as well as offering up some clues as to how they can be tackled.

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Regular exercise isn’t always possible for everyone, especially in older age, and further down the line, there might be a way to develop drugs that offer the same cognitive protection as exercise without any movement involved.

It’s going to be a long while yet before we get to that stage – much more research and safety testing will be required first – but we now know much more about the brain-boosting powers that come along with exercise.

“We’re uncovering biology that Alzheimer’s research has largely overlooked,” says Villeda. “It may open new therapeutic possibilities beyond the traditional strategies that focus almost exclusively on the brain.”

The research has been published in Cell.