Insights into the use of biomarkers in clinical trials in Alzheimer's disease

Abstract

Biomarkers have been instrumental in population selection and disease monitoring in clinical trials of recently FDA-approved drugs targeting amyloid-β to slow the progression of Alzheimer's disease (AD). As new therapeutic strategies and biomarker techniques emerge, the importance of biomarkers in drug development is growing exponentially. In this emerging landscape, biomarkers are expected to serve a wide range of contexts of use in clinical trials focusing on AD and related dementias. The joint FDA-NIH BEST (Biomarkers, EndpointS, and other Tools) framework provides standardised terminology to facilitate communication among stakeholders in this increasingly complex field. This review explores various applications of biomarkers relevant to AD clinical trials, using the BEST resource as a reference. For simplicity, we predominantly provide contextual characterizations of biomarkers use from the perspective of drugs targeting amyloid-β and tau proteins. However, general definitions and concepts can be extrapolated to other targets.

Keywords: Alzheimer's disease; BEST glossary; Biomarkers; Clinical trials; Disease-modifying therapies.

Fig. 1

Biomarkers profile predictive of anti-Aβ therapy benefit. A (Aβ); P (tau Phosphorylation), T (tau Tangle) N (Neurodegeneration). Green = pathological burden.