Table 2.7.

FDA terminology for biomarkers and identification of biomarkers in each category for AD drug development (adapted from Amur et al. [103])

FDA biomarker type	Examples for drug development	Examples from AD drug development
Diagnostic biomarkers	Patient selection	Positive amyloid imaging Low CSF Aβ42 or change in Aβ/tau or Aβ/p-tau ratio
Prognostic biomarkers	Stratify patients or enrich trials with patients likely to have disease	Tau PET to identify AD patients likely to have more rapid cognitive progression ApoE-4 carriers as a prognostic marker for ARIA in immunotherapy programs
Predictive biomarkers	Stratification Enrichment/inclusion criteria Enrichment/companion diagnostic	Use of tau PET to identify AD patients more likely to respond to anti-tau therapies
Response biomarkers	Pharmacodynamic biomarker as an indicator of intended drug activity Efficacy response biomarker as a surrogate for a clinical endpoint	Target engagement biomarkers (e.g., reduction in amyloid plaque in anti-amyloid programs) Markers of disease modification (e.g., drug-placebo differences in CSF total tau, FDG PET hypometabolism, or MRI atrophy)
Safety biomarkers	Biomarkers to detect adverse and off-target drug responses	MRI to monitor for ARIA in immunotherapy programs

ApoE apolipoprotein E, ARIA amyloid-related imaging abnormalities, CSF cerebrospinal fluid, FDG fluorodeoxyglucose, MRI magnetic resonance imaging, PET positron-emission tomography