In individuals with autosomal dominant Alzheimer’s disease, plasma neurofilament light chain levels increase approximately 18.9 years before estimated symptom onset, and cerebrospinal fluid neurofilament light chain levels increase approximately 24.6 years before symptom onset, demonstrating that cerebrospinal fluid neurofilament light chain elevation precedes plasma neurofilament light chain elevation in the presymptomatic phase.

When nerve fibers in the brain are damaged, they break open and release a protein called neurofilament light chain into the fluid surrounding the brain. This fluid drains directly into the spinal fluid, where the protein builds up first. Over time, some of this protein slowly crosses from the brain into the bloodstream, but it takes longer to appear in the blood than in the spinal fluid. Once the damage becomes severe, the rate at which the protein enters the blood slows down, so the blood levels stop rising even though the brain damage keeps getting worse.