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A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology

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 p...

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Autores principales: Abe, Koji, Shang, Jingwei, Shi, Xiaowen, Yamashita, Toru, Hishikawa, Nozomi, Takemoto, Mami, Morihara, Ryuta, Nakano, Yumiko, Ohta, Yasuyuki, Deguchi, Kentaro, Ikeda, Masaki, Ikeda, Yoshio, Okamoto, Koichi, Shoji, Mikio, Takatama, Masamitsu, Kojo, Motohisa, Kuroda, Takeshi, Ono, Kenjiro, Kimura, Noriyuki, Matsubara, Etsuro, Osakada, Yosuke, Wakutani, Yosuke, Takao, Yoshiki, Higashi, Yasuto, Asada, Kyoichi, Senga, Takehito, Lee, Lyang-Ja, Tanaka, Kenji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029318/
https://www.ncbi.nlm.nih.gov/pubmed/31771070
http://dx.doi.org/10.3233/JAD-191016
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author Abe, Koji
Shang, Jingwei
Shi, Xiaowen
Yamashita, Toru
Hishikawa, Nozomi
Takemoto, Mami
Morihara, Ryuta
Nakano, Yumiko
Ohta, Yasuyuki
Deguchi, Kentaro
Ikeda, Masaki
Ikeda, Yoshio
Okamoto, Koichi
Shoji, Mikio
Takatama, Masamitsu
Kojo, Motohisa
Kuroda, Takeshi
Ono, Kenjiro
Kimura, Noriyuki
Matsubara, Etsuro
Osakada, Yosuke
Wakutani, Yosuke
Takao, Yoshiki
Higashi, Yasuto
Asada, Kyoichi
Senga, Takehito
Lee, Lyang-Ja
Tanaka, Kenji
author_facet Abe, Koji
Shang, Jingwei
Shi, Xiaowen
Yamashita, Toru
Hishikawa, Nozomi
Takemoto, Mami
Morihara, Ryuta
Nakano, Yumiko
Ohta, Yasuyuki
Deguchi, Kentaro
Ikeda, Masaki
Ikeda, Yoshio
Okamoto, Koichi
Shoji, Mikio
Takatama, Masamitsu
Kojo, Motohisa
Kuroda, Takeshi
Ono, Kenjiro
Kimura, Noriyuki
Matsubara, Etsuro
Osakada, Yosuke
Wakutani, Yosuke
Takao, Yoshiki
Higashi, Yasuto
Asada, Kyoichi
Senga, Takehito
Lee, Lyang-Ja
Tanaka, Kenji
author_sort Abe, Koji
collection PubMed
description 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 Aβ(1 - 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.
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spelling pubmed-70293182020-03-04 A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology Abe, Koji Shang, Jingwei Shi, Xiaowen Yamashita, Toru Hishikawa, Nozomi Takemoto, Mami Morihara, Ryuta Nakano, Yumiko Ohta, Yasuyuki Deguchi, Kentaro Ikeda, Masaki Ikeda, Yoshio Okamoto, Koichi Shoji, Mikio Takatama, Masamitsu Kojo, Motohisa Kuroda, Takeshi Ono, Kenjiro Kimura, Noriyuki Matsubara, Etsuro Osakada, Yosuke Wakutani, Yosuke Takao, Yoshiki Higashi, Yasuto Asada, Kyoichi Senga, Takehito Lee, Lyang-Ja Tanaka, Kenji J Alzheimers Dis Research Article 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 Aβ(1 - 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. IOS Press 2020-01-07 /pmc/articles/PMC7029318/ /pubmed/31771070 http://dx.doi.org/10.3233/JAD-191016 Text en © 2020 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY 4.0) License (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Abe, Koji
Shang, Jingwei
Shi, Xiaowen
Yamashita, Toru
Hishikawa, Nozomi
Takemoto, Mami
Morihara, Ryuta
Nakano, Yumiko
Ohta, Yasuyuki
Deguchi, Kentaro
Ikeda, Masaki
Ikeda, Yoshio
Okamoto, Koichi
Shoji, Mikio
Takatama, Masamitsu
Kojo, Motohisa
Kuroda, Takeshi
Ono, Kenjiro
Kimura, Noriyuki
Matsubara, Etsuro
Osakada, Yosuke
Wakutani, Yosuke
Takao, Yoshiki
Higashi, Yasuto
Asada, Kyoichi
Senga, Takehito
Lee, Lyang-Ja
Tanaka, Kenji
A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology
title A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology
title_full A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology
title_fullStr A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology
title_full_unstemmed A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology
title_short A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology
title_sort new serum biomarker set to detect mild cognitive impairment and alzheimer’s disease by peptidome technology
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029318/
https://www.ncbi.nlm.nih.gov/pubmed/31771070
http://dx.doi.org/10.3233/JAD-191016
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