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Review
. 2020 Jul 24;10(3):68.
doi: 10.3390/jpm10030068.

Use of Biomarkers in Ongoing Research Protocols on Alzheimer's Disease

Marco Canevelli  1   2 , Giulia Remoli  1 , Ilaria Bacigalupo  2 , Martina Valletta  1 , Marco Toccaceli Blasi  1 , Francesco Sciancalepore  1 , Giuseppe Bruno  1 , Matteo Cesari  3   4 , Nicola Vanacore  2
Affiliations
Review

Use of Biomarkers in Ongoing Research Protocols on Alzheimer's Disease

Marco Canevelli et al. J Pers Med. .

Abstract

The present study aimed to describe and discuss the state of the art of biomarker use in ongoing Alzheimer's disease (AD) research. A review of 222 ongoing phase 1, 2, 3, and 4 protocols registered in the clinicaltrials.gov database was performed. All the trials (i) enrolling subjects with clinical disturbances and/or preclinical diagnoses falling within the AD continuum; and (ii) testing the efficacy and/or safety/tolerability of a therapeutic intervention, were analyzed. The use of biomarkers of amyloid deposition, tau pathology, and neurodegeneration among the eligibility criteria and/or study outcomes was assessed. Overall, 58.2% of ongoing interventional studies on AD adopt candidate biomarkers. They are mostly adopted by studies at the preliminary stages of the drug development process to explore the safety profile of novel therapies, and to provide evidence of target engagement and disease-modifying properties. The biologically supported selection of participants is mostly based on biomarkers of amyloid deposition, whereas the use of biomarkers as study outcomes mostly relies on markers of neurodegeneration. Biomarkers play an important role in the design and conduction of research protocols targeting AD. Nevertheless, their clinical validity, utility, and cost-effectiveness in the "real world" remain to be clarified.

Keywords: Alzheimer’s disease; biomarkers; clinical trials; diagnostic research; drug development.

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Conflict of interest statement

Authors have no conflicts of interest to disclose for the present study.

Figures

Figure 1
Figure 1
Flow-chart of protocols’ selection.
Figure 2
Figure 2
Biomarkers adopted to ascertain eligibility in the selected protocols (n = 62) according to the AT (N) grouping. Data are shown as %. A: aggregated Aβ or associated pathologic state; T: aggregated tau (neurofibrillary tangles) or associated pathologic state; N: neurodegeneration or neuronal injury. Colors refer to AT (N) biomarker grouping: blue: A; purple: T; orange: N.
Figure 3
Figure 3
Biomarkers adopted as primary or secondary outcomes in the selected protocols (n = 66) according to the AT (N) grouping. Data are shown as %. A: aggregated Aβ or associated pathologic state; T: aggregated tau (neurofibrillary tangles) or associated pathologic state; N: neurodegeneration or neuronal injury. Colors refer to AT (N) biomarker grouping blue: A; purple: T; orange: N.
See this image and copyright information in PMC

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