Combating Alzheimer’s through incremental discoveries

In efforts to combat Alzheimer’s disease, neuroscientist Beth Stevens has revolutionized the perception of microglial cells, which act as the brain’s immune defense.

Microglia survey the brain for indications of illness or trauma, assisting in the removal of deceased or impaired cells and selectively trimming synapses, which facilitate communication among neurons.

However, this mechanism is not flawless.

The Stevens Lab, situated at Boston Children’s Hospital and the Broad Institute of MIT and Harvard, has established that erroneous pruning can contribute to Alzheimer’s, Huntington’s disease, and other conditions.

Stevens’ discoveries have laid the groundwork for novel medications aimed at combating neurodegenerative diseases and for new biomarkers to identify illnesses at earlier stages. This research holds the potential to influence treatment for the approximately 7 million Americans affected by Alzheimer’s. As the U.S. demographic ages, the annual incidence is projected to double by 2050, according to the nonprofit Alzheimer’s Association, potentially escalating care expenses from $360 million to $1 trillion.

“We could never have progressed without the foundational science and inquiry-driven research from the outset.” 

When she began her career in the early 2000s, Stevens, presently an associate professor of neurology at Harvard Medical School, had no foresight as to where her curiosity would lead.

“I was merely pursuing the science,” she remarked. “It was a fascinating new domain where the brain’s immune system was contributing to the shaping of synapses and circuits during standard development.”

She suspected the potential drawbacks of pruning — and her hunch was validated. Essential backing from federal entities aided her in following her path.

“The essence of our research, from my postdoctoral years to the initial decade of my lab, was predominantly propelled by the National Institutes of Health and other governmental funding,” she explained.

This foundational research does not always yield a definitive resolution, noted Stevens, who was recognized as a MacArthur “genius” for her work on microglia in 2015. “Someone who doesn’t consider disease implications might say, ‘Oh, Stevens Lab is focused on the visual system of a mouse. They’re attempting to grasp how the visual system of a mouse is wired.’ It can seem as though that’s so far removed from potential translation to anything meaningful. Who cares how a mouse perceives?”

However, these investigations enable scientists to explore queries they cannot in humans, she emphasized — which paves the way for new revelations, leading to improved understandings of diseases and subsequently to treatments that enhance human existence. 

“Our microglial study,” Stevens stated, “is an excellent illustration of an immune-related pathway and cell type that we could never have advanced without the foundational science and inquiry-driven research from the beginning.”