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Abe, Koji Department of Neurology, Okayama University Kaken ID publons researchmap
Shang, Jingwei Department of Neurology, Okayama University
Shi, Xiaowen Department of Neurology, Okayama University
Yamashita, Toru Department of Neurology, Okayama University ORCID Kaken ID researchmap
Hishikawa, Nozomi Department of Neurology, Okayama University Kaken ID
Takemoto, Mami Department of Neurology, Okayama University ORCID Kaken ID
Morihara, Ryuta Department of Neurology, Okayama University
Nakano, Yumiko Department of Neurology, Okayama University ORCID
Ohta, Yasuyuki Department of Neurology, Okayama University Kaken ID researchmap
Deguchi, Kentaro Department of Neurology, Okayama City Hospital, Okayama ORCID Kaken ID publons
Ikeda, Masaki Department of Neurology, Gunma University, Graduate School of Medicine
Ikeda, Yoshio Department of Neurology, Gunma University, Graduate School of Medicine
Okamoto, Koichi Department of Neurology, Geriatrics Research Institute and Hospital
Shoji, Mikio Department of Neurology, Geriatrics Research Institute and Hospital
Takatama, Masamitsu Department of Neurology, Geriatrics Research Institute and Hospital
Kojo, Motohisa Department of Neurology, Ako Chuo Hospital
Kuroda, Takeshi Division of Neurology, Department of Medicine, Showa University, School of Medicine
Ono, Kenjiro Division of Neurology, Department of Medicine, Showa University, School of Medicine
Kimura, Noriyuki Department of Neurology, Faculty of Medicine, Oita University
Matsubara, Etsuro Department of Neurology, Faculty of Medicine, Oita University
Osakada, Yosuke Department of Neurology, Kurashiki Heisei Hospital ORCID
Wakutani, Yosuke Department of Neurology, Kurashiki Heisei Hospital
Takao, Yoshiki Department of Neurology, Kurashiki Heisei Hospital
Higashi, Yasuto Department of Neurology, Himeji Central Hospital
Asada, Kyoichi Membrane Protein and Ligand Analysis Center, Protosera Inc.,
Senga, Takehito Membrane Protein and Ligand Analysis Center, Protosera Inc.,
Lee, Lyang-Ja Membrane Protein and Ligand Analysis Center, Protosera Inc.,
Tanaka, Kenji Membrane Protein and Ligand Analysis Center, Protosera Inc., Kaken ID publons researchmap
Abstract
Background:
Because dementia is an emerging problem in the world, biochemical markers of cerebrospinal fluid (CSF) and radio-isotopic analyses are helpful for diagnosing Alzheimer’s disease (AD). Although blood sample is more feasible and plausible than CSF or radiological biomarkers for screening potential AD, measurements of serum amyloid- β (Aβ), plasma tau, and serum antibodies for Aβ1 - 42 are not yet well established.
Objective:
We aimed to identify a new serum biomarker to detect mild cognitive impairment (MCI) and AD in comparison to cognitively healthy control by a new peptidome technology.
Methods:
With only 1.5μl of serum, we examined a new target plate “BLOTCHIP®” plus a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) to discriminate control (n = 100), MCI (n = 60), and AD (n = 99). In some subjects, cognitive Mini-Mental State Examination (MMSE) were compared to positron emission tomography (PET) with Pittsburgh compound B (PiB) and the serum probability of dementia (SPD). The mother proteins of candidate serum peptides were examined in autopsied AD brains.
Results:
Apart from Aβ or tau, the present study discovered a new diagnostic 4-peptides-set biomarker for discriminating control, MCI, and AD with 87% of sensitivity and 65% of specificity between control and AD (***p < 0.001). MMSE score was well correlated to brain Aβ deposition and to SPD of AD. The mother proteins of the four peptides were upregulated for coagulation, complement, and plasticity (three proteins), and was downregulated for anti-inflammation (one protein) in AD brains.
Conclusion:
The present serum biomarker set provides a new, rapid, non-invasive, highly quantitative and low-cost clinical application for dementia screening, and also suggests an alternative pathomechanism of AD for neuroinflammation and neurovascular unit damage.
Keywords
Alzheimer’s disease
biomarker
coagulation
complement
MALDI-TOF
mild cognitive impairment
neuroinflammation
peptidome
plasticity
Published Date
2020-01-07
Publication Title
Journal of Alzheimer's Disease
Volume
volume73
Issue
issue1
Publisher
IOP Press
Start Page
217
End Page
227
ISSN
1387-2877
NCID
AA11545428
Content Type
Journal Article
language
English
OAI-PMH Set
岡山大学
Copyright Holders
© 2020 - IOS Press and the authors.
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isVersionOf https://content.iospress.com/articles/journal-of-alzheimers-disease/jad191016
License
https://creativecommons.org/licenses/by/4.0/
Funder Name
Japan Agency for Medical Research and Development
助成番号
7211700176
7211700180
7211700095