Amyotrophic lateral sclerosis (ALS) is currently incurable and causes the progressive loss of nerve cells that control our muscles. However, the disease can differ considerably between patients: in some, nerve cells in the brain are predominantly affected, whereas in others, degeneration is more pronounced in the brainstem and spinal cord. The biological basis of these differences remains poorly understood.
In this project, the scientists will analyze tissue from several regions of the brain and spinal cord from the same ALS patients. Using modern single-cell technologies, they will investigate changes in nerve cells and their supporting cells, with a particular focus on microglia, the immune cells of the brain. They will also use naturally occurring changes in mitochondrial DNA as cellular “fingerprints” to trace related cell populations. The aim is to understand why ALS develops differently between patients and to identify molecular features that may ultimately contribute to more precise diagnosis.