MAPT and Alzheimer disease: Examples of pathophysiological response wet biomarkers that have been used in early phase NDD DMT trials include quantification of CSF tau phosphorylated at threonine 181 (p-tau181) [54,60] and evaluation of amyloid β by PET [75] for Alzheimer’s disease pathology, phosphorylated neurofilament heavy chains (and post-hoc neurofilament light chain) concentrations as general axonal damage biomarker in ALS [33], FTD [129], and Huntington’s disease [131], and CSF mitochondrial dysfunction markers (GDF15, lactate) in MS [139] (Table 2).