The FDA-NIH BEST framework defines monitoring biomarkers as a “biomarker that can be measured repeatedly for assessing status of a disease or medical condition or for evidence of exposure to (or effect of) a medical product or an environmental agent”.55 Consistent with previous longitudinal studies in older adults with MCI and AD,33,68,69 we found that an increase in plasma NfL level was associated with a longitudinal decline in global cognition. This evidence concerns the gene NEFL and Alzheimer disease.