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


Authors: Yamamoto-Imoto, H.; Zamolodchikov, D.; Chen, Z. L.; Bourne, S. L.; Rizvi, S.; Singh, P.; Norris, E. H.; Weis-Garcia, F.; Strickland, S.
Article Title: A novel detection method of cleaved plasma high-molecular-weight kininogen reveals its correlation with Alzheimer's pathology and cognitive impairment
Abstract: 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. © 2018 The Authors
Keywords: diagnosis; dementia; alzheimer's disease; cleaved hmw kininogen; contact system activation; hmw kininogen; plasma biomarker; sandwich elisa
Journal Title: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Volume: 10
ISSN: 2352-8729
Publisher: Elsevier Inc.  
Date Published: 2018-01-01
Start Page: 480
End Page: 489
Language: English
DOI: 10.1016/j.dadm.2018.06.008
PROVIDER: scopus
PMCID: PMC6178129
PUBMED: 30310850
DOI/URL:
Notes: Article -- Export Date: 1 November 2018 -- Source: Scopus
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MSK Authors
  1. Sam Lloyd Bourne
    1 Bourne
  2. Syeda Rizvi
    1 Rizvi