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Review
. 2024 Oct:108:105322.
doi: 10.1016/j.ebiom.2024.105322. Epub 2024 Oct 3.

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

Tharick A Pascoal  1 , Cristiano S Aguzzoli  2 , Firoza Z Lussier  3 , Lucía Crivelli  4 , Claudia K Suemoto  5 , Juan Fortea  6 , Pedro Rosa-Neto  7 , Eduardo R Zimmer  8 , Pamela C L Ferreira  3 , Bruna Bellaver  3
Affiliations
Review

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

Tharick A Pascoal et al. EBioMedicine. 2024 Oct.

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.

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Conflict of interest statement

Declaration of interests TAP received support to attend meetings from the Alzheimer's Association. LC has received support to attend meetings from the Alzheimer's Association and IMPACT-AD. CKS has received support to attend meetings from the Alzheimer's Association and payment for lectures from the Busse Research Award for Biomedical Research. CSA has received support to attend meetings from the Alzheimer's Association. JF reported receiving personal fees for service on the advisory boards, adjudication committees, or speaker honoraria from AC Immune, Adamed, Alzheon, Biogen, Esteve, Laboratorios Carnot, Ionis, Lilly, LMI, Lundbeck, Perha, Roche, Zambon and, outside the submitted work. JF reports holding a patent for markers of synaptopathy in neurodegenerative disease (licence to Adx, EPI8382175.0). PR-N received payment for lectures and has served on scientific advisory boards and/or as a consultant for Novo Nordisk, and Eisai. ERZ is on the scientific advisory board of Nintx, Novo Nordisk and is on the scientific advisory board and is a co-founder of MASIMA. MASIMA is a Brazilian company that provides brain scan analytical tools to hospitals. ERZ has never received royalties of financial gains from MASIMA. ERZ has received support to attend meetings from Alzheimer's Association, CNPq, and CAPES. PCLF has received support to attend meetings from the Alzheimer's Association. BB has received support to attend meetings from the Alzheimer's Association.

Figures

Fig. 1
Fig. 1
Biomarkers profile predictive of anti-Aβ therapy benefit. A (Aβ); P (tau Phosphorylation), T (tau Tangle) N (Neurodegeneration). Green = pathological burden.
See this image and copyright information in PMC

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