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β-Secretase1 biological markers for Alzheimer’s disease: state-of-art of validation and qualification

β-Secretase1 (BACE1) protein concentrations and rates of enzyme activity, analyzed in human bodily fluids, are promising candidate biological markers for guidance in clinical trials investigating BACE1 inhibitors to halt or delay the dysregulation of the amyloid-β pathway in Alzheimer’s disease (AD)...

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Autores principales: Hampel, Harald, Lista, Simone, Vanmechelen, Eugeen, Zetterberg, Henrik, Giorgi, Filippo Sean, Galgani, Alessandro, Blennow, Kaj, Caraci, Filippo, Das, Brati, Yan, Riqiang, Vergallo, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566058/
https://www.ncbi.nlm.nih.gov/pubmed/33066807
http://dx.doi.org/10.1186/s13195-020-00686-3
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author Hampel, Harald
Lista, Simone
Vanmechelen, Eugeen
Zetterberg, Henrik
Giorgi, Filippo Sean
Galgani, Alessandro
Blennow, Kaj
Caraci, Filippo
Das, Brati
Yan, Riqiang
Vergallo, Andrea
author_facet Hampel, Harald
Lista, Simone
Vanmechelen, Eugeen
Zetterberg, Henrik
Giorgi, Filippo Sean
Galgani, Alessandro
Blennow, Kaj
Caraci, Filippo
Das, Brati
Yan, Riqiang
Vergallo, Andrea
author_sort Hampel, Harald
collection PubMed
description β-Secretase1 (BACE1) protein concentrations and rates of enzyme activity, analyzed in human bodily fluids, are promising candidate biological markers for guidance in clinical trials investigating BACE1 inhibitors to halt or delay the dysregulation of the amyloid-β pathway in Alzheimer’s disease (AD). A robust body of evidence demonstrates an association between cerebrospinal fluid/blood BACE1 biomarkers and core pathophysiological mechanisms of AD, such as brain protein misfolding and aggregration, neurodegeneration, and synaptic dysfunction. In pharmacological trials, BACE1 candidate biomarkers may be applied to a wide set of contexts of use (CoU), including proof of mechanism, dose-finding, response and toxicity dose estimation. For clinical CoU, BACE1 biomarkers show good performance for prognosis and disease prediction. The roadmap toward validation and qualification of BACE1 biomarkers requires standardized pre-analytical and analytical protocols to reduce inter-site variance that may have contributed to inconsistent results. BACE1 biomarker-drug co-development programs, including biomarker-guided outcomes and endpoints, may support the identification of sub-populations with a higher probability to benefit from BACE1 inhibitors with a reduced risk of adverse effects, in line with the evolving precision medicine paradigm.
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spelling pubmed-75660582020-10-20 β-Secretase1 biological markers for Alzheimer’s disease: state-of-art of validation and qualification Hampel, Harald Lista, Simone Vanmechelen, Eugeen Zetterberg, Henrik Giorgi, Filippo Sean Galgani, Alessandro Blennow, Kaj Caraci, Filippo Das, Brati Yan, Riqiang Vergallo, Andrea Alzheimers Res Ther Review β-Secretase1 (BACE1) protein concentrations and rates of enzyme activity, analyzed in human bodily fluids, are promising candidate biological markers for guidance in clinical trials investigating BACE1 inhibitors to halt or delay the dysregulation of the amyloid-β pathway in Alzheimer’s disease (AD). A robust body of evidence demonstrates an association between cerebrospinal fluid/blood BACE1 biomarkers and core pathophysiological mechanisms of AD, such as brain protein misfolding and aggregration, neurodegeneration, and synaptic dysfunction. In pharmacological trials, BACE1 candidate biomarkers may be applied to a wide set of contexts of use (CoU), including proof of mechanism, dose-finding, response and toxicity dose estimation. For clinical CoU, BACE1 biomarkers show good performance for prognosis and disease prediction. The roadmap toward validation and qualification of BACE1 biomarkers requires standardized pre-analytical and analytical protocols to reduce inter-site variance that may have contributed to inconsistent results. BACE1 biomarker-drug co-development programs, including biomarker-guided outcomes and endpoints, may support the identification of sub-populations with a higher probability to benefit from BACE1 inhibitors with a reduced risk of adverse effects, in line with the evolving precision medicine paradigm. BioMed Central 2020-10-16 /pmc/articles/PMC7566058/ /pubmed/33066807 http://dx.doi.org/10.1186/s13195-020-00686-3 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Hampel, Harald
Lista, Simone
Vanmechelen, Eugeen
Zetterberg, Henrik
Giorgi, Filippo Sean
Galgani, Alessandro
Blennow, Kaj
Caraci, Filippo
Das, Brati
Yan, Riqiang
Vergallo, Andrea
β-Secretase1 biological markers for Alzheimer’s disease: state-of-art of validation and qualification
title β-Secretase1 biological markers for Alzheimer’s disease: state-of-art of validation and qualification
title_full β-Secretase1 biological markers for Alzheimer’s disease: state-of-art of validation and qualification
title_fullStr β-Secretase1 biological markers for Alzheimer’s disease: state-of-art of validation and qualification
title_full_unstemmed β-Secretase1 biological markers for Alzheimer’s disease: state-of-art of validation and qualification
title_short β-Secretase1 biological markers for Alzheimer’s disease: state-of-art of validation and qualification
title_sort β-secretase1 biological markers for alzheimer’s disease: state-of-art of validation and qualification
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566058/
https://www.ncbi.nlm.nih.gov/pubmed/33066807
http://dx.doi.org/10.1186/s13195-020-00686-3
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