1. A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology
- Author
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Yumiko Nakano, Masamitsu Takatama, Kyoichi Asada, Mikio Shoji, Takeshi Kuroda, Motohisa Kojo, Mami Takemoto, Yasuto Higashi, Yoshiki Takao, Yoshio Ikeda, Toru Yamashita, Noriyuki Kimura, Koichi Okamoto, Kentaro Deguchi, Ryuta Morihara, Jingwei Shang, Nozomi Hishikawa, Yasuyuki Ohta, Takehito Senga, Yosuke Osakada, Koji Abe, Kenji Tanaka, Kenjiro Ono, Yosuke Wakutani, Etsuro Matsubara, Lyang Ja Lee, Masaki Ikeda, and Xiaowen Shi
- Subjects
0301 basic medicine ,Oncology ,Male ,Disease ,neuroinflammation ,chemistry.chemical_compound ,0302 clinical medicine ,Cerebrospinal fluid ,Reference Values ,complement ,Aged, 80 and over ,Aniline Compounds ,medicine.diagnostic_test ,biology ,General Neuroscience ,General Medicine ,Middle Aged ,Mental Status and Dementia Tests ,Psychiatry and Mental health ,Clinical Psychology ,Positron emission tomography ,Biomarker (medicine) ,biomarker ,Female ,Antibody ,Alzheimer’s disease ,Research Article ,MALDI-TOF ,medicine.medical_specialty ,Amyloid ,tau Proteins ,03 medical and health sciences ,mild cognitive impairment ,Alzheimer Disease ,Predictive Value of Tests ,Internal medicine ,mental disorders ,medicine ,peptidome ,Dementia ,Humans ,Cognitive Dysfunction ,coagulation ,Aged ,Amyloid beta-Peptides ,business.industry ,medicine.disease ,Thiazoles ,030104 developmental biology ,chemistry ,plasticity ,Positron-Emission Tomography ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,biology.protein ,Geriatrics and Gerontology ,Pittsburgh compound B ,business ,Peptides ,030217 neurology & neurosurgery ,Biomarkers - 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 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.
- Published
- 2020