Blocking a Cell's Waste Crew Sparks Tau Fibres in Mice
Graded Preliminary — experiments in neurons, mice and 52 human brain samples; the findings come from short-term laboratory manipulation and have not been tested in living people.
Animal study. Findings may not carry over to people, which is why the grade is capped at Preliminary.
- Design
- Lab study
- Participants
- 52
- Duration
- —
- Funding
- US National Institutes of Health, National Science Foundation, US Department…
Blocking a protein-clearing machine on the nerve cell surface triggers twisted tau fibres in cultured neurons and mouse brains.
In Alzheimer's disease, the protein tau twists into fine paired fibres inside nerve cells. What flips that switch has been unclear. Researchers now point to a waste-disposal machine that sits on the outer skin of nerve cells and breaks down proteins. When they blocked it selectively, tau fibres soon formed in cultured nerve cells and, within three days, in mouse brains. Under the electron microscope the fibres looked like those taken from human Alzheimer's brains.
The story then turned to APOE, the strongest known inherited risk factor for Alzheimer's. It comes in three versions. Nerve cells carrying the risk version E4 had less of this waste machinery on their surface. They built up clumped tau once only about 20 percent of its activity was gone. Cells with the protective version E2 held out until about 85 percent was blocked. In mice the amount also fell from around 12 months of age. In brain tissue from 52 deceased people, carriers of two E4 copies had less of it too.
The work rests on cells, mice and tissue samples. The authors note that a short, sharp block does not reproduce the slow, widespread disease.
Conflict of Interest Disclosure: One author is named on a patent for the inhibitors used and received funding from Eli Lilly; another has company equity and advisory roles in Alzheimer's-related firms.
Disclaimer: Research summaries are provided for informational purposes only and do not constitute medical advice. Always consult a qualified healthcare professional before making changes to your health routine.