Abstract

A blood-based biomarker able to track early neurodegeneration in Alzheimer’s disease would be valuable. Serum neurofilament-light (NfL) is elevated in familial Alzheimer’s disease (FAD) mutation carriers prior to symptom onset, but exactly how early NfL becomes abnormal and whether it can track change within individuals is uncertain.

We recruited 18 symptomatic carriers of autosomal dominant FAD mutations, 19 presymptomatic carriers, and 11 non-carriers. Blood was taken at baseline, and 26 participants also gave at least one follow-up sample (mean interval=2.5 years). Serum NfL was measured on the SIMOA platform. A longitudinal mixed effects framework was used to model change in NfL over time.

Serum NfL was increased (p<0.05) in mutation carriers compared with non-carriers 11 years before the estimated time of symptom onset, with rate of change in NfL becoming significantly different 12 years before. However, there was high variability in the inter-individual rate of change in NfL between participants.

Serum NfL concentration, and its rate of change, are sensitive, at the group level at least, to very early AD-neurodegenration. However, the high variability between individuals in NfL rate of change may make it difficult at present to use this measure to track early change in individual patients.