MAPT and early-onset autosomal dominant Alzheimer disease: Andersson et al. identify that high Aβ42/Aβ40 ratios in brain protofibrils best predict lower Aβ42/Aβ40 ratios in the cerebrospinal fluid (CSF) and higher neurofilament light/total tau levels, indicating that CSF changes in Alzheimer’s disease reflect soluble protofibrils more accurately than amyloid plaques.