PSEN1 and Alzheimer disease: Our finding of a presymptomatic increase in serum NfL in FAD mutation carriers contrasts with findings from familial amyotrophic lateral sclerosis (ALS), where no increase was detected until after symptom onset despite symptomatic ALS participants having much higher concentrations than has been detected in either familial or sporadic AD.25 This likely reflects differences in the underlying biology and temporal pattern of neurodegeneration in AD vs ALS.