A nerve cell is like a house where the lights are never switched off, just dimmed to emergency mode: the bulbs grow faint, but life still flickers. In ALS, such house-cells turn up in the spinal cord, and for the first time scientists have watched them shift into that mode.
Scientists took samples of brain and spinal cord tissue from 36 veterans: 12 with ALS and the harmful protein, 12 with ALS without it, and 12 healthy ones. They measured proteins in individual nerve cells using a laser that cuts out the area around each cell. In total, they processed about 3500 cells. It turned out that in the spinal cord, cells switch on an aging program in both forms of ALS, while in the brain this happens only when the harmful protein is present. It's as if a house went into emergency mode for different reasons, but the result is the same: the lights grow dim.
It used to be unclear why some patients live longer without the harmful protein. Now it's clear that cell aging is a shared mechanism, and the protein merely amplifies it. If aging makes cells vulnerable, one could try to clear out the senescent cells or suppress their signals. Drugs that kill senescent cells have already helped mice with similar diseases. For ALS this is still a hypothesis, but if we learn to bring the bright light back to these cells, their residents will have a chance.
Senescent neurons are rare: in the human brain they make up just 2–3% of all cells. To catch such one-of-a-kind cells, the team had to measure proteins in individual neurons rather than in a chunk of tissue, where their signal gets lost among thousands of other cells.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.