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beta-Secretase1 biological markers for Alzheimer's disease : state-of-art of validation and qualification

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Abstract
beta -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-beta 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.
Keywords
AMYLOID-PRECURSOR PROTEIN, BETA-SECRETASE BACE1, CEREBROSPINAL-FLUID, PP-BETA, BIOMARKER, RISK, TAU, GENERATION, EXPRESSION, CORRELATE, Alzheimer's disease, Amyloid-beta pathway, Axonal damage, BACE1, Clinical trials, Context of use, Fluid biomarkers, Neurodegeneration

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MLA
Hampel, Harald, et al. “Beta-Secretase1 Biological Markers for Alzheimer’s Disease : State-of-Art of Validation and Qualification.” ALZHEIMERS RESEARCH & THERAPY, vol. 12, no. 1, 2020, doi:10.1186/s13195-020-00686-3.
APA
Hampel, H., Lista, S., Vanmechelen, E., Zetterberg, H., Giorgi, F. S., Galgani, A., … Depypere, H. (2020). beta-Secretase1 biological markers for Alzheimer’s disease : state-of-art of validation and qualification. ALZHEIMERS RESEARCH & THERAPY, 12(1). https://doi.org/10.1186/s13195-020-00686-3
Chicago author-date
Hampel, Harald, Simone Lista, Eugeen Vanmechelen, Henrik Zetterberg, Filippo Sean Giorgi, Alessandro Galgani, Kaj Blennow, et al. 2020. “Beta-Secretase1 Biological Markers for Alzheimer’s Disease : State-of-Art of Validation and Qualification.” ALZHEIMERS RESEARCH & THERAPY 12 (1). https://doi.org/10.1186/s13195-020-00686-3.
Chicago author-date (all authors)
Hampel, Harald, Simone Lista, Eugeen Vanmechelen, Henrik Zetterberg, Filippo Sean Giorgi, Alessandro Galgani, Kaj Blennow, Filippo Caraci, Brati Das, Riqiang Yan, Andrea Vergallo, - APMI, and Herman Depypere. 2020. “Beta-Secretase1 Biological Markers for Alzheimer’s Disease : State-of-Art of Validation and Qualification.” ALZHEIMERS RESEARCH & THERAPY 12 (1). doi:10.1186/s13195-020-00686-3.
Vancouver
1.
Hampel H, Lista S, Vanmechelen E, Zetterberg H, Giorgi FS, Galgani A, et al. beta-Secretase1 biological markers for Alzheimer’s disease : state-of-art of validation and qualification. ALZHEIMERS RESEARCH & THERAPY. 2020;12(1).
IEEE
[1]
H. Hampel et al., “beta-Secretase1 biological markers for Alzheimer’s disease : state-of-art of validation and qualification,” ALZHEIMERS RESEARCH & THERAPY, vol. 12, no. 1, 2020.
@article{8701599,
  abstract     = {{beta -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-beta 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.}},
  articleno    = {{130}},
  author       = {{Hampel, Harald and Lista, Simone and Vanmechelen, Eugeen and Zetterberg, Henrik and Giorgi, Filippo Sean and Galgani, Alessandro and Blennow, Kaj and Caraci, Filippo and Das, Brati and Yan, Riqiang and Vergallo, Andrea and APMI, - and Depypere, Herman}},
  issn         = {{1758-9193}},
  journal      = {{ALZHEIMERS RESEARCH & THERAPY}},
  keywords     = {{AMYLOID-PRECURSOR PROTEIN,BETA-SECRETASE BACE1,CEREBROSPINAL-FLUID,PP-BETA,BIOMARKER,RISK,TAU,GENERATION,EXPRESSION,CORRELATE,Alzheimer's disease,Amyloid-beta pathway,Axonal damage,BACE1,Clinical trials,Context of use,Fluid biomarkers,Neurodegeneration}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{14}},
  title        = {{beta-Secretase1 biological markers for Alzheimer's disease : state-of-art of validation and qualification}},
  url          = {{http://dx.doi.org/10.1186/s13195-020-00686-3}},
  volume       = {{12}},
  year         = {{2020}},
}

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