Table 2.1.

Roles of biomarkers in AD drug development with examples

Role in trial	Biology identified	Fluid biomarker	Brain imaging
Diagnosis and participant identification	Presence of AD-type pathological changes	Low CSF Aβ42 or CSF Aβ42/t-tau ratio or Aβ42/p-tau ratio	Positive amyloid imaging
Target engagement	Reduction of amyloid production	Reduced Aβ42 production as shown by SILK
	Removal of aggregated Aβ		Reduced Aβ aggregation as shown by amyloid imaging
Support for disease modification	Reduction of measures of neurodegeneration compared to placebo	Reduced CSF t-tau	Drug-placebo difference in favor of active treatment for FDG PET hypometabolism or MRI atrophy
Analytic stratification	Identification of ApoE-4 carrier status	ApoE genotype
Analytic stratification	Effects on the liver or blood	Blood liver function tests, complete blood count
	Production of ARIA by monoclonal antibodies		MRI monitoring for ARIA

Aβ42 amyloid beta protein 42 amino acid length fragment, AD Alzheimer’s disease, ApoE apolipoprotein E, ARIA amyloid-related imaging abnormalities, CSF cerebrospinal fluid, FDG fluorodeoxyglucose, MRI magnetic resonance imaging, PET positron-emission tomography, SILK stable isotope labeling kinetics