In 1965, microbiologists brought back a soil sample from Easter Island, from which a substance later named rapamycin was isolated. It was first used against fungi, then found to slow aging in mice. Now the same drug appears to be able to repair the brain's vascular system damaged by Alzheimer's disease.
The vessels lose the ability to dilate when neurons need more oxygen. As a result, the brain starves, and microbleeds appear in its tissue. Nine out of ten patients with this disease are found to have such vascular damage. Researchers tested whether this process could be halted by suppressing the mTOR protein, which controls cell growth and protein accumulation.
Mice with an Alzheimer's disease model were given rapamycin in their food starting at four months of age. By eighteen months, the animals that received the drug had 40.6% less area of vascular amyloid deposits than the control group. At the same time, plaques in the brain tissue itself were unchanged: the drug acted specifically on the vessels.
This is an important twist: vascular disturbances arise earlier than neuron death, and they may be what sets off the chain of damage. In mice that received rapamycin, vessels began to dilate again in response to a chemical signal, even if amyloid remained in their walls. The barrier between blood and brain became tighter: dye molecules that previously leaked into the brain were now held back. The number of microbleeds fell to the level of healthy animals.
Memory in the mice was tested as follows: they were placed in a chamber where they received a mild electric shock, and later researchers watched whether they froze in fear upon returning to the same chamber. Ordinary mice with Alzheimer's disease did not remember the danger, while those that received rapamycin froze just like healthy ones. The brain once again received oxygen on time, and this restored the animals' ability to remember.
Rapamycin turned out to be a traffic officer who clears amyloid jams from the brain's vascular highways. It does not restore neurons that have already died, but it helps preserve the roads that deliver oxygen to them. If this approach works in humans, doctors will have a tool to intervene at an early stage, when the vascular network can still be repaired.
Rapamycin was discovered in a soil sample from Easter Island and was initially used as an antifungal agent, later becoming known as a geroprotector that extends the lifespan of mice.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.