A groundbreaking study has revealed a drug that may protect the brain’s critical defenses—and prevent memory loss—by targeting a long-overlooked culprit in Alzheimer’s disease: the blood-brain barrier. This discovery could usher in an entirely new strategy for treating neurodegenerative disorders.
Key Points at a Glance
- Researchers developed a drug that protects the blood-brain barrier in Alzheimer’s models
- The treatment preserved cognition and prevented neurodegeneration in mice
- Targeting enzyme 15-PGDH may be key to stopping brain inflammation
- The approach differs from current amyloid-focused Alzheimer’s treatments
- The drug also showed protective effects after traumatic brain injury
For decades, Alzheimer’s research has zeroed in on neurons and the accumulation of toxic amyloid plaques. But a team of scientists at Case Western Reserve University and its partners has taken a radically different route—one that could reshape the future of Alzheimer’s treatment.
In a new study published in Proceedings of the National Academy of Sciences (PNAS), researchers describe a drug that doesn’t target neurons or amyloid, but instead protects a vital line of defense often ignored: the blood-brain barrier (BBB). This network of cells is essential for keeping harmful substances out of the brain while allowing nutrients in. Its breakdown has long been recognized as a warning sign in Alzheimer’s, but few therapies have focused directly on it—until now.
“Our findings suggest an effective new way to safely prevent neurodegeneration and cognitive impairment in Alzheimer’s disease by directly protecting the blood-brain barrier,” said Andrew Pieper, co-lead author and professor of translational psychiatry at Case Western Reserve.
The team’s target was an enzyme called 15-PGDH, which is highly concentrated in the BBB. In both human and mouse models of Alzheimer’s and traumatic brain injury (TBI), this enzyme was found to be elevated—and detrimental. It weakens the barrier’s integrity, allowing inflammatory factors to flood the brain, contributing to cell damage and memory decline.
To counter this, the researchers used a drug called SW033291, originally developed to stimulate tissue repair in colitis and bone marrow transplant recovery. Repurposed in this study, the compound was found to block 15-PGDH activity in the BBB. The results in Alzheimer’s mouse models were striking: complete protection of the BBB, no signs of neurodegeneration, and full preservation of memory and learning abilities.
Crucially, this protection came without altering amyloid levels in the brain. That’s important because the most recent FDA-approved Alzheimer’s drugs focus exclusively on removing amyloid—but have shown only modest results and come with significant risks. SW033291 offers a new route, one that sidesteps amyloid and focuses instead on preserving the brain’s natural defenses.
“This is a completely new approach,” said Sanford Markowitz, co-lead investigator and professor of cancer genetics. “We’re not trying to clean up after the disease. We’re strengthening the brain’s ability to protect itself in the first place.”
The research didn’t stop with Alzheimer’s. The same protective effects were observed when the drug was administered to mice after traumatic brain injury—even 24 hours after the event—suggesting it could have broader applications in treating concussions or other neuroinflammatory conditions.
While human trials are still needed, the drug’s proven safety profile in earlier studies offers a head start. The scientists believe that targeting the BBB and the inflammatory role of 15-PGDH could open doors not just for Alzheimer’s, but for a range of neurodegenerative and neurological disorders.
As the global population ages, with more than 55 million people already living with dementia, the need for novel therapies has never been more urgent. This study brings hope—hope rooted not in chasing toxic proteins, but in reinforcing the brain’s own barriers.
Source: Case Western Reserve University
