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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2020
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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. |
format | Online Article Text |
id | pubmed-7029318 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
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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