Suzuki Itsuku, Noguchi Miwa, Arito Mitsumi, Sato Toshiyuki, Omoteyama Kazuki, Maedomari Mioto, Hasegawa Hiroshi, Suematsu Naoya, Okamoto Kazuki, Kato Tomohiro, Yamaguchi Noboru, Kurokawa Manae S
Department of Neuropsychiatry, St. Marianna University School of Medicine, Kawasaki, Japan.
Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
Int J Geriatr Psychiatry. 2015 Dec;30(12):1195-206. doi: 10.1002/gps.4274. Epub 2015 Mar 6.
For diagnosis of dementia with Lewy bodies (DLB), we tried to find blood biomarkers for the disease.
Serum peptides were comprehensively detected by mass spectrometry. Peptides of interest were identified by tandem mass spectrometry.
One hundred forty-six peptides were detected in a training set consisting of 30 DLB patients, 30 patients with Alzheimer's disease (AD), and 28 healthy control (HC) subjects. Multivariate analysis for discriminating the DLB group from the non-DLB (AD and HC) group using ion intensity of four peptides (2898, 4052, 4090, and 5002 m/z) showed sensitivity of 93.3% and specificity of 87.9% (DLB/nonDLB-4P model). In a testing set consisting of 20 DLB patients, 30 AD patients, and 14 HC subjects, this model showed sensitivity of 90.0% and specificity of 88.6%. DLB/nonDLB-4P model detected 86.7% and 90.0% of the AD patients as non-DLB in the training and testing sets, respectively, and discriminated all the 15 patients with amnestic mild cognitive impairment as non-DLB. Notably, a combination of two peptides (1737 and 5002 m/z) showed sensitivity of 95.0% and specificity of 93.3% for discriminating the DLB group from the AD group (DLB/nonDLB-2P model) in the testing set. The peptides used in these models included fragments from complement 4b, Wnt-2b, and lipopolysaccharide-binding protein, which were reported to be involved in the pathology of DLB or Parkinson's disease and hippocampal neurogenesis.
Serum peptide profiles would provide useful DLB biomarker candidates, which may be implicated in the pathophysiology of the disease.
为了诊断路易体痴呆（DLB），我们试图寻找该疾病的血液生物标志物。
通过质谱全面检测血清肽。通过串联质谱鉴定感兴趣的肽。
在一个由30例DLB患者、30例阿尔茨海默病（AD）患者和28例健康对照（HC）受试者组成的训练集中检测到146种肽。使用四种肽（2898、4052、4090和5002 m/z）的离子强度对DLB组与非DLB（AD和HC）组进行多变量分析，结果显示敏感性为93.3%，特异性为87.9%（DLB/非DLB - 4P模型）。在一个由20例DLB患者、30例AD患者和14例HC受试者组成的测试集中，该模型显示敏感性为90.0%，特异性为88.6%。DLB/非DLB - 4P模型在训练集和测试集中分别将86.7%和90.0%的AD患者检测为非DLB，并将所有15例遗忘型轻度认知障碍患者鉴别为非DLB。值得注意的是，在测试集中，两种肽（1737和5002 m/z）的组合对区分DLB组和AD组显示出95.0%的敏感性和93.3%的特异性（DLB/非DLB - 2P模型）。这些模型中使用的肽包括补体4b、Wnt - 2b和脂多糖结合蛋白的片段，据报道这些片段与DLB或帕金森病的病理以及海马神经发生有关。
血清肽谱将提供有用的DLB生物标志物候选物，这些候选物可能与该疾病的病理生理学有关。
