In individuals with autosomal dominant Alzheimer’s disease, elevated levels of neurofilament light chain in cerebrospinal fluid and plasma are associated with a faster rate of gray matter atrophy during symptomatic stages, but not with the extent of amyloid-beta accumulation, indicating a temporal decoupling between amyloid deposition and neurodegeneration.

When nerve fibers in the brain are damaged, they break down and release a protein called neurofilament light chain into the fluid around the brain. This protein enters the bloodstream, where it can be measured. The amount of this protein rising over time matches how fast brain tissue shrinks, but it does not match how much sticky amyloid protein has built up. The amyloid buildup happens early and stops increasing, while the nerve damage and tissue loss keep getting worse on their own.