The increase in CSF NfL level with solanezumab treatment is, however, directionally consistent with cognitive worsening reported in the DIAN-TU-001 study20 and with the numerically greater cognitive decline observed in A4 in preclinical sAD.60 The reasons for increases of NfL level and cognitive decline are unclear, as a meta-analysis of the Trial of Solanezumab for Mild Dementia Due to Alzheimer’s Disease (EXPEDITION) 2 and 3 trials has found modest cognitive improvement in mildly symptomatic AD with solanezumab.61 Differences in the stage of disease could be one possible explanation. Here, NEFL is linked to early-onset autosomal dominant Alzheimer disease.