Compounds broke down an activated brain protein in aged mice
Bloodstream delivery in aged Alzheimer's-model mice also reduced amyloid deposits and abnormal changes to tau protein, and improved cognition.
Limit: Adverse effects were not reported in the abstract
Edited by Boris Djordjevic · AgingResearch.News
In an animal experiment, aged APP/PS1 mice, a model of Alzheimer's disease, received compounds designed to cross the blood-brain barrier and break down an activated brain protein. This barrier controls passage from blood into the brain. The compounds targeted activated death-associated protein kinase 1, an enzyme known as DAPK1.
The compounds used a ring-shaped molecular carrier to enter the brain through a transport pathway that becomes more active with age. A chemical switch enabled activation only within Alzheimer's disease lesions rich in reactive oxygen molecules. Delivery through the bloodstream reduced activated DAPK1 and deposits of amyloid-beta protein. It also reduced tau hyperphosphorylation, the excessive attachment of phosphate groups to the tau protein. The researchers also reported improved cognition.
Why it matters
Age-related changes in the blood-brain barrier complicate drug delivery for neurodegenerative diseases. This work suggests a way to design protein-removing compounds that take advantage of those changes.
Caveats
These animal experiments do not establish benefits in people. The abstract did not report animal numbers, doses, treatment duration or adverse effects.
The paper
Southwest Jiaotong University
Journal of the American Chemical Society, Sep 30, 2026
