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A novel detection method of cleaved plasma high-molecular-weight kininogen reveals its correlation with Alzheimer's pathology and cognitive impairment

INTRODUCTION: Accumulation of β-amyloid is a pathological hallmark of Alzheimer's disease (AD). β-Amyloid activates the plasma contact system leading to kallikrein-mediated cleavage of intact high-molecular-weight kininogen (HKi) to cleaved high-molecular-weight kininogen (HKc). Increased HKi c...

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Autores principales: Yamamoto-Imoto, Hitomi, Zamolodchikov, Daria, Chen, Zu-Lin, Bourne, S. Lloyd, Rizvi, Syeda, Singh, Pradeep, Norris, Erin H., Weis-Garcia, Frances, Strickland, Sidney
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178129/
https://www.ncbi.nlm.nih.gov/pubmed/30310850
http://dx.doi.org/10.1016/j.dadm.2018.06.008
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author Yamamoto-Imoto, Hitomi
Zamolodchikov, Daria
Chen, Zu-Lin
Bourne, S. Lloyd
Rizvi, Syeda
Singh, Pradeep
Norris, Erin H.
Weis-Garcia, Frances
Strickland, Sidney
author_facet Yamamoto-Imoto, Hitomi
Zamolodchikov, Daria
Chen, Zu-Lin
Bourne, S. Lloyd
Rizvi, Syeda
Singh, Pradeep
Norris, Erin H.
Weis-Garcia, Frances
Strickland, Sidney
author_sort Yamamoto-Imoto, Hitomi
collection PubMed
description INTRODUCTION: Accumulation of β-amyloid is a pathological hallmark of Alzheimer's disease (AD). β-Amyloid activates the plasma contact system leading to kallikrein-mediated cleavage of intact high-molecular-weight kininogen (HKi) to cleaved high-molecular-weight kininogen (HKc). Increased HKi cleavage is observed in plasma of AD patients and mouse models by Western blot. For potential diagnostic purposes, a more quantitative method that can measure HKc levels in plasma with high sensitivity and specificity is needed. METHODS: HKi/c, HKi, and HKc monoclonal antibodies were screened from hybridomas using direct ELISA with a fluorescent substrate. RESULTS: We generated monoclonal antibodies recognizing HKi or HKc specifically and developed sandwich ELISAs that can quantitatively detect HKi and HKc levels in human. These new assays show that decreased HKi and increased HKc levels in AD plasma correlate with dementia and neuritic plaque scores. DISCUSSION: High levels of plasma HKc could be used as an innovative biomarker for AD.
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spelling pubmed-61781292018-10-11 A novel detection method of cleaved plasma high-molecular-weight kininogen reveals its correlation with Alzheimer's pathology and cognitive impairment Yamamoto-Imoto, Hitomi Zamolodchikov, Daria Chen, Zu-Lin Bourne, S. Lloyd Rizvi, Syeda Singh, Pradeep Norris, Erin H. Weis-Garcia, Frances Strickland, Sidney Alzheimers Dement (Amst) Blood-Based Biomarkers INTRODUCTION: Accumulation of β-amyloid is a pathological hallmark of Alzheimer's disease (AD). β-Amyloid activates the plasma contact system leading to kallikrein-mediated cleavage of intact high-molecular-weight kininogen (HKi) to cleaved high-molecular-weight kininogen (HKc). Increased HKi cleavage is observed in plasma of AD patients and mouse models by Western blot. For potential diagnostic purposes, a more quantitative method that can measure HKc levels in plasma with high sensitivity and specificity is needed. METHODS: HKi/c, HKi, and HKc monoclonal antibodies were screened from hybridomas using direct ELISA with a fluorescent substrate. RESULTS: We generated monoclonal antibodies recognizing HKi or HKc specifically and developed sandwich ELISAs that can quantitatively detect HKi and HKc levels in human. These new assays show that decreased HKi and increased HKc levels in AD plasma correlate with dementia and neuritic plaque scores. DISCUSSION: High levels of plasma HKc could be used as an innovative biomarker for AD. Elsevier 2018-08-04 /pmc/articles/PMC6178129/ /pubmed/30310850 http://dx.doi.org/10.1016/j.dadm.2018.06.008 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Blood-Based Biomarkers
Yamamoto-Imoto, Hitomi
Zamolodchikov, Daria
Chen, Zu-Lin
Bourne, S. Lloyd
Rizvi, Syeda
Singh, Pradeep
Norris, Erin H.
Weis-Garcia, Frances
Strickland, Sidney
A novel detection method of cleaved plasma high-molecular-weight kininogen reveals its correlation with Alzheimer's pathology and cognitive impairment
title A novel detection method of cleaved plasma high-molecular-weight kininogen reveals its correlation with Alzheimer's pathology and cognitive impairment
title_full A novel detection method of cleaved plasma high-molecular-weight kininogen reveals its correlation with Alzheimer's pathology and cognitive impairment
title_fullStr A novel detection method of cleaved plasma high-molecular-weight kininogen reveals its correlation with Alzheimer's pathology and cognitive impairment
title_full_unstemmed A novel detection method of cleaved plasma high-molecular-weight kininogen reveals its correlation with Alzheimer's pathology and cognitive impairment
title_short A novel detection method of cleaved plasma high-molecular-weight kininogen reveals its correlation with Alzheimer's pathology and cognitive impairment
title_sort novel detection method of cleaved plasma high-molecular-weight kininogen reveals its correlation with alzheimer's pathology and cognitive impairment
topic Blood-Based Biomarkers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178129/
https://www.ncbi.nlm.nih.gov/pubmed/30310850
http://dx.doi.org/10.1016/j.dadm.2018.06.008
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