Neuronal pentraxin receptor in cerebrospinal fluid as a potential biomarker for neurodegenerative diseases.
Neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by progressive loss of cognitive function, dementia, and problems with movements. In order to find new protein biomarkers of high specificity from cerebrospinal fluid (CSF) of AD and PD patients, one-dimensional gel electrophoresis (1-DE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) as well as 2-DE analysis were performed. In 1-DE and LC-MS/MS 371 proteins were identified, among which levels of proteins such as isoform 1 of contactin-1, contactin-2, carnosine dipeptidase 1 (CNDP1), 120 kDa isoform precursor of neural cell adhesion molecule 1 (NCAM-120), alpha-dystroglycan, secreted protein acidic and rich in cysteine-like protein 1 precursor (SPARCL1), isoform 2 of calsyntenin 1 (CLSTN1), and neuronal pentraxin receptor (NPR) showed significant changes in AD or PD CSF compared with normal subjects. In 2-DE analysis approximately 747-915 spots were detected in CSF of AD or PD patients, from which 17-24 proteins with more than a 1.2 fold change were identified by tandem MS. Most proteins identified showed consistent changes in LC-MS/MS and 2-DE analysis. Three proteins that showed significant changes were selected for further validation by Western blot analysis. While NCAM-120 and alpha-dystroglycan exhibited higher levels in both AD and PD CSF compared with normal subjects, the level of NPR was increased only in AD CSF in Western blot analysis. The results were consistent with quantitative analysis of 2-DE spots. A higher level of NPR was also found in AD serum. This study suggests that NCAM-120, alpha-dystroglycan, and NPR are candidate biomarkers in CSF for neurodegenerative diseases, and that the changes in the CSF level of NPR may be specific for AD.
Yin
Guo Nan
GN
Department of Pharmacology, Brain Science and Engineering Institute, CMRI, Kyungpook National University School of Medicine, Joong-Gu, Daegu, South Korea.
Lee
Ho Won
HW
Cho
Je-Yoel
JY
Suk
Kyoungho
K
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000134:cerebrospinal fluid* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000134:cerebrospinal fluid; D015816:Cell Adhesion Molecules, Neuronal / Q000134:cerebrospinal fluid; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid*; D058967:Contactin 1; D058969:Contactin 2; D058966:Contactins; D004150:Dipeptidases / Q000134:cerebrospinal fluid; D049030:Dystroglycans / Q000134:cerebrospinal fluid; D015180:Electrophoresis, Gel, Two-Dimensional; D016326:Extracellular Matrix Proteins / Q000134:cerebrospinal fluid; D006801:Humans; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000097:blood / Q000134:cerebrospinal fluid* / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000134:cerebrospinal fluid; D010300:Parkinson Disease / Q000134:cerebrospinal fluid*; D020033:Protein Isoforms / Q000134:cerebrospinal fluid; D053719:Tandem Mass Spectrometry; D000099153:Pentraxins
D015415:Biomarkers; D002097:C-Reactive Protein; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D058967:Contactin 1; D058969:Contactin 2; D058966:Contactins; D004150:Dipeptidases; D049030:Dystroglycans; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D020033:Protein Isoforms; D000099153:Pentraxins; C503225:CLSTN1 protein, human; C548669:CNTN1 protein, human; C548674:CNTN2 protein, human; C483081:DAG1 protein, human; C503126:SPARCL1 protein, human; C522928:CNDP1 protein, human