Elevated plasma neurofilament light in aging reflects brain white-matter alterations but does not predict cognitive decline or Alzheimer's disease.

Introduction: We investigated neurofilament light (NFL) accumulation in normal aging as well as in preclinical and clinical Alzheimer's disease (AD) and assessed individual differences in NFL load in relation to cognition and brain white-matter integrity.

Methods: We analyzed longitudinal data covering 30 years (1988-2017). Cognitive testing was done up to six times. Plasma NFL was quantified for controls and 142 cases who developed AD over time, and longitudinal changes in NFL were quantified for 100 individuals with three brain-imaging sessions.

Results: Longitudinal analyses revealed age-related NFL increases with marked variability. AD cases had elevated NFL levels, while no significant group differences were seen in the preclinical phase. Variability in NFL levels showed non-significant correlations with cognition but was associated with brain white matter.

Discussion: Our findings suggest that elevated blood NFL, likely reflecting brain white-matter alterations, characterizes clinical AD, while NFL levels do not predict age-related cognitive impairment or impending AD.