Could a person’s sex dictate how his or her brain reacts to amyloid? Stephen Ferguson, University of Ottawa Brain and Mind Institute, Canada, thinks it may. In a paper published December 15 in Science Signaling, his group reported that Aβ bound to the mGluR5 metabotropic glutamate receptor in postmortem brain tissue from men but not women. The scientists found the same in mice. Why might that be? It turns out that mGluR5 and the cellular prion protein, which form a trimeric complex with Aβ, do not bind each other in the female brain. The reason for this binding deficiency remains elusive. If confirmed, it would highlight the importance of sex-specific biology for understanding and treating Alzheimer’s disease.
- Aβ binds metabotropic glutamate receptors in males but not females.
- Estrogen does not explain the difference, but cellular prion protein may.
- PrP-Aβ-mGluR complexes form only in male mice.
“I was fascinated—I would never expect these fundamental protein mechanisms to be different in male and female brains,” said Helmut Kessels, University of Amsterdam, Netherlands.