Immune cells normally fight infections. In people with Alzheimer’s, many of these cells are found inside the brain. Scientists think they may help the disease get worse, but they did not know where the cells came from.
A new study from Washington University in St. Louis looked at mice. The researchers discovered that T‑cells get a signal from lymph nodes (small organs outside the brain). This signal tells them to move into the brain and cause damage. When the scientists blocked the signal, the brain stayed healthier.
The work was published on September 3 in Nature Neuroscience. It shows a new immune pathway that could be used to slow or stop the damage seen in Alzheimer’s and other tau‑related diseases.
An Immune Route Outside the Brain
"Treating brain diseases is hard because medicines must cross the blood‑brain barrier," said researcher Hol Holtzman. "But we might not need to get drugs inside the brain at all. We can change T‑cells, which are already used in other diseases, to help the brain instead."
Finding Where T Cells Come From
Holtzman's lab has shown before that removing T‑cells from the brain protects mice from damage caused by tau protein. The next question was: where do those T‑cells start?
Some T‑cells need help from dendritic cells to know what to attack. The brain has very few of the special dendritic cells called cDC1, and those that are there do not seem to work with the T‑cells that appear after tau tangles form.
This suggested that both the dendritic cells and the T‑cell activation happen outside the brain.
Stopping the Signal Saves the Brain
To test this idea, the scientists removed dendritic cells from the lymph nodes of mice that normally develop tau tangles. The result was clear: far fewer T‑cells entered the brain, and the brain damage was much smaller. The amount of tau tangles did not change, but the mice kept their memory and learning abilities.
How Damage Might Call the Immune System
Researchers still do not know the exact message that tells dendritic cells to wake up T‑cells. One guess is that damaged brain cells release pieces of themselves. These pieces travel to lymph nodes in the neck, where dendritic cells recognize them and tell T‑cells to attack.
New Ways to Treat Alzheimer’s
Because this immune pathway works outside the brain, it offers several new targets for medicine. Holtzman's team is now testing whether blocking dendritic cells in middle age (when tau tangles first appear) can give the same protection they saw when the cells were blocked from birth.
They also want to find the exact signal that guides T‑cells to the brain. If they can stop that signal, they might keep harmful immune cells from reaching brain tissue.
"Not long ago, many of us did not think the immune system mattered for diseases like Alzheimer’s," Holtzman said. "Now we see dendritic cells are important, and they could become a future treatment target."