A Novel Peptidome Technology for the Diagnosis of Mild Cognitive Impairment and Alzheimer's Disease by Selected Reaction Monitoring

被引:0
|
作者
Fukui, Yusuke [1 ]
Tadokoro, Koh [1 ]
Hamada, Minaki [2 ]
Asada, Kyoichi [2 ]
Lee, Lyang-Ja [2 ]
Tachiki, Hidehisa [2 ]
Morihara, Ryuta [1 ]
Abe, Koji [3 ]
Yamashita, Toru [1 ]
机构
[1] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol, Kitaku, Okayama, Japan
[2] Protosera Inc, KENTO Innovat Pk NK, Settsu, Osaka, Japan
[3] Natl Ctr Neurol & Psychiat, Dept Neurol, Kodaira, Tokyo, Japan
关键词
Alzheimer's disease; biochemical marker; dementia risk test; liquid chromatography-MS/MS; mild cognitive impairment; peptidome; selected reaction monitoring; ASSOCIATION WORKGROUPS; NATIONAL INSTITUTE; FIBRINOGEN; COMPLEMENT; RECOMMENDATIONS; GUIDELINES; EXPRESSION; BIOMARKER; SERUM;
D O I
10.3233/JAD-230915
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: With the aging of populations worldwide, Alzheimer's disease (AD) has become a concern due to its high prevalence and the continued lack of established treatments. Early diagnosis is required as a preventive intervention to modify the disease's progression. In our previous study, we performed peptidomic analysis of serum samples obtained from AD patients and age-matched healthy subjects to seek peptide biomarker candidates for AD by using BLOTCHIP (R)-MS analysis, and identified four peptides as AD biomarker candidates. Objective: The objective was to validate the serum biomarker peptides to distinguish mild cognitive impairment (MCI) and AD in comparison to cognitively healthy controls using a new peptidome technology, the Dementia Risk Test. Methods: We enrolled 195 subjects with normal cognitive function (NC; n = 70), MCI (n = 55), and AD (n = 70), The concentrations of cognitive impairment marker peptides (Fibrinogen alpha chain (FAC), Fibrinogen beta chain (FBC), Plasma protease C1 inhibitor (PPC1I), alpha 2-HS-glycoprotein (AHSG)) were quantified by using a selected reaction monitoring assay based on liquid chromatography-MS/MS. Results: The present study confirmed that three peptides, FAC, FBC, and PPC1I, were significantly upregulated during the onset of AD. This three-peptide set was both highly sensitive in determining AD (sensitivity: 85.7%, specificity: 95.7%, AUC: 0.900) and useful in distinguishing MCI (sensitivity: 61.8%, specificity: 98.6%, AUC: 0.824) from NC. Conclusions: In this validation study, we confirmed the high diagnostic potential of the three peptides identified in our previous study as candidate serum biomarkers for AD. The Dementia Risk Test may be a powerful tool for detecting AD-related pathological changes.
引用
收藏
页码:219 / 228
页数:10
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