These markers are increasingly close to integration into clinical pathways in AD: for example, early reductions in the amyloid-β (Aβ) 42:40 ratio and elevation in phospho-tau species (eg, phosphorylated at serine 181, p-tau181 and tau phosphorylated at threonine 217, p-tau217) are sensitive to amyloid pathology.14 15 Neurodegeneration may be indexed by increased levels of total tau, or the axonal marker plasma neurofilament light (NfL). This evidence concerns the gene NEFL and Alzheimer disease.