Overview
- UCSF scientists report in Cell that the liver enzyme GPLD1, elevated by exercise, signals to brain blood vessels to bolster barrier function.
- In aged mice, GPLD1 trimmed excess TNAP from blood–brain barrier cells, reducing leakiness and improving performance on memory tasks.
- Boosting TNAP in young mice induced barrier breakdown and cognitive decline, while genetically lowering TNAP in old mice reversed these effects.
- A TNAP inhibitor (SBI-425) replicated barrier and cognitive benefits in aged mice and reduced amyloid plaque density and nesting deficits in an Alzheimer’s model.
- Postmortem human tissue showed higher vascular TNAP in Alzheimer’s disease, underscoring a translational lead that will require targeted, safety-tested therapies.