From: The “rights” of precision drug development for Alzheimer’s disease
Role in trial | Examples of biomarker used |
---|---|
Identification of trial population | Presence of presenilin 1 (PS1), presenilin 2 (PS2), or amyloid precursor protein (APP) mutations; ApoE-4 plus TOMM40; trisomy 21 |
Confirmation of diagnosis; exclude non-AD diagnoses | Amyloid imaging; CSF AD signature |
Prognosis and course projection | In MCI, ApoE-4 carriers progress more rapidly |
Amyloid production and clearance (target engagement) | Stable isotope-labeled kinetics (SILK); BACE activity reduction with BACE inhibitor; CSF Aβ reduction by BACE inhibitor or gamma-secretase inhibitor |
Impact of therapy on brain circuit and network function | fMRI; EEG |
Impact of therapy on intermediate targets | Amyloid imaging; CSF amyloid; tau PET; CSF phospho-tau |
Disease modification | MRI atrophy; CSF total tau; FDG PET; neurofilament light |
Stratification for trial analysis | ApoE-4 genotype |
Side effect monitoring | MRI surveillance for amyloid-related imaging abnormalities (ARIA); liver function tests; complete blood counts; electrocardiography |