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

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  • Additional Information
    • Source:
      Publisher: IOS Press Country of Publication: Netherlands NLM ID: 9814863 Publication Model: Print Cited Medium: Internet ISSN: 1875-8908 (Electronic) Linking ISSN: 13872877 NLM ISO Abbreviation: J Alzheimers Dis Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam ; Washington : IOS Press, c1998-
    • Subject Terms:
      Alzheimer Disease/*blood ; Biomarkers/*blood ; Cognitive Dysfunction/*blood ; Peptides/*blood; Aged ; Aged, 80 and over ; Alzheimer Disease/psychology ; Amyloid beta-Peptides/blood ; Aniline Compounds ; Cognitive Dysfunction/psychology ; Female ; Humans ; Male ; Mental Status and Dementia Tests ; Middle Aged ; Positron-Emission Tomography ; Predictive Value of Tests ; Reference Values ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Thiazoles ; tau Proteins/blood
    • 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.
    • References:
      Biochem Biophys Res Commun. 2009 Jan 30;379(1):110-4. (PMID: 19073144)
      Cancer. 1950 Jan;3(1):32-5. (PMID: 15405679)
      J Intern Med. 2004 Sep;256(3):183-94. (PMID: 15324362)
      Eur J Neurosci. 2016 Jan;43(1):3-16. (PMID: 26332448)
      J Alzheimers Dis. 2011;24(2):327-33. (PMID: 21239851)
      Br J Psychiatry. 1982 Jun;140:566-72. (PMID: 7104545)
      J Alzheimers Dis. 2016 Apr 12;52(4):1311-9. (PMID: 27079724)
      Neurol Sci. 2018 May;39(5):909-918. (PMID: 29508099)
      Neurology. 1984 Jul;34(7):939-44. (PMID: 6610841)
      Neuroscience. 2019 Sep 15;416:126-136. (PMID: 31394196)
      Lifetime Data Anal. 2007 Dec;13(4):497-512. (PMID: 18000755)
      J Neurosci Res. 2011 Jun;89(6):815-21. (PMID: 21394760)
      Neurology. 1993 Nov;43(11):2412-4. (PMID: 8232972)
      Brain Res. 1995 Mar 27;675(1-2):75-82. (PMID: 7796155)
      J Alzheimers Dis. 2016 Jun 13;53(3):893-905. (PMID: 27314529)
      J Psychiatr Res. 1975 Nov;12(3):189-98. (PMID: 1202204)
      J Cereb Blood Flow Metab. 2017 Mar;37(3):877-889. (PMID: 27117856)
      PLoS One. 2015 Oct 13;10(10):e0140311. (PMID: 26461913)
      Hum Mol Genet. 2017 Oct 1;26(19):3808-3822. (PMID: 28934394)
      Proteomics. 2011 Jul;11(13):2727-37. (PMID: 21630454)
      J Neuroinflammation. 2011 Aug 09;8:93. (PMID: 21827691)
      J Gastroenterol. 2018 Nov;53(11):1179-1185. (PMID: 29497816)
      Nat Neurosci. 2019 Jul;22(7):1089-1098. (PMID: 31235908)
      Geriatr Gerontol Int. 2016 Apr;16(4):458-65. (PMID: 25952646)
      Ann Neurol. 1998 Jul;44(1):17-26. (PMID: 9667589)
      Nat Biotechnol. 2009 Jul;27(7):633-41. (PMID: 19561596)
      J Neurol Sci. 2016 Jan 15;360:141-52. (PMID: 26723991)
      Geriatr Gerontol Int. 2017 Nov;17(11):1907-1913. (PMID: 28261965)
      J Alzheimers Dis. 2019;68(4):1667-1675. (PMID: 30958362)
      Clin Chem. 2005 Oct;51(10):1933-45. (PMID: 16099937)
      Mol Neurodegener. 2011 Mar 06;6(1):20. (PMID: 21375782)
      Clin Neurol Neurosurg. 2017 Sep;160:111-115. (PMID: 28715708)
      Biomed Res Int. 2014;2014:908636. (PMID: 25050378)
      Neurobiol Dis. 2014 Dec;72 Pt A:117-22. (PMID: 24825318)
      Nature. 2011 Jul 13;475(7355):S2-4. (PMID: 21760579)
      Neurosci Res. 2019 Jun;143:61-70. (PMID: 29885344)
      Neuroreport. 2016 Oct 19;27(15):1114-9. (PMID: 27541273)
      Alzheimers Dement. 2017 Dec;13(12):1327-1336. (PMID: 28602601)
      Sci Rep. 2015 Jun 17;5:11412. (PMID: 26081315)
      J Alzheimers Dis. 2010;22(2):345-55. (PMID: 20847441)
      Nature. 2018 Feb 8;554(7691):249-254. (PMID: 29420472)
      Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21812-7. (PMID: 21098282)
      J Alzheimers Dis. 2016 Mar 5;52(1):113-26. (PMID: 27060955)
      Proteomics. 2005 Dec;5(18):4713-8. (PMID: 16281180)
      Alzheimers Res Ther. 2017 Dec 11;9(1):96. (PMID: 29229003)
      Geriatr Gerontol Int. 2017 Jun;17(6):951-958. (PMID: 27215917)
      Neurodegener Dis Manag. 2019 Aug;9(4):193-203. (PMID: 31099300)
      Mol Neurodegener. 2017 Sep 4;12(1):63. (PMID: 28866979)
      Bioanalysis. 2015 Dec;7(23):2991-3004. (PMID: 26626236)
      Eur J Nucl Med Mol Imaging. 2017 May;44(5):850-857. (PMID: 27966045)
      Alzheimers Dement (Amst). 2016 Dec 22;6:11-20. (PMID: 28138509)
      J Thromb Haemost. 2009 Jul;7 Suppl 1:146-50. (PMID: 19630788)
    • Contributed Indexing:
      Keywords: Alzheimer’s disease; MALDI-TOF; biomarker; coagulation; complement; mild cognitive impairment; neuroinflammation; peptidome; plasticity
    • Accession Number:
      0 (2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole)
      0 (Amyloid beta-Peptides)
      0 (Aniline Compounds)
      0 (Biomarkers)
      0 (MAPT protein, human)
      0 (Peptides)
      0 (Thiazoles)
      0 (tau Proteins)
    • Publication Date:
      Date Created: 20191128 Date Completed: 20210419 Latest Revision: 20210419
    • Publication Date:
      20221213
    • Accession Number:
      PMC7029318
    • Accession Number:
      10.3233/JAD-191016
    • Accession Number:
      31771070