It may well be the case that markers of neurodegeneration such as NfL may be stronger predictors of decline in already cognitively impaired populations15,17,19,44–49 (or in populations at very high genetic risk of decline34), and further work is needed to understand which blood-based biomarkers of AD pathobiology are most informative at different stages of disease. This evidence concerns the gene NEFL and Alzheimer disease.