Plasma Levels of Complement 4a Protein are Increased in Alzheimer's Disease

被引:32
作者
Bennett, Stuart [1 ]
Grant, Melissa [2 ]
Creese, Andrew J. [2 ,3 ]
Mangialasche, Francesca [4 ]
Cecchetti, Roberta [4 ]
Cooper, Helen J. [3 ]
Mecocci, Patrizia [4 ]
Aldred, Sarah [1 ]
机构
[1] Univ Birmingham, Sch Sport & Exercise Sci, Birmingham B15 2TT, W Midlands, England
[2] Univ Birmingham, Sch Dent, Birmingham B15 2TT, W Midlands, England
[3] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England
[4] Univ Hosp, Inst Gerontol & Geriatr, Perugia, Italy
关键词
Alzheimer's disease; iTRAQ; proteomics; biomarker; mass spectrometry; CEREBROSPINAL-FLUID PROTEINS; PROTEOMIC IDENTIFICATION; INFLAMMATORY MARKERS; SERUM PROTEOME; BIOMARKERS; INTERLEUKIN-6; ACTIVATION; DEMENTIA; BRAIN; ATHEROSCLEROSIS;
D O I
10.1097/WAD.0b013e318239dcbd
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Alzheimer's disease (AD) is a devastating neurodegenerative disorder that has been predicted to affect 106.2 million people worldwide by 2050. Currently, definitive diagnosis for this disease is given post mortem, and there is a need for biomarker identification to enable earlier diagnosis of this disease. Biomarkers of AD would ideally represent early disease process and will be present in peripheral tissue before cognitive decline develops in this population. Proteomic technologies offer a strategy to undertake such work. In recent times, research in this field has moved away from classical 2-dimensional gel-based proteomics toward more sensitive, non-gel-based proteomic methodologies. In the study presented here, isobaric labeling for relative and absolute quantification was used to assess plasma protein expression in a small group of AD and control samples. Several proteins were identified as being differentially expressed between these 2 populations. Complement 4a plasma protein was identified as increased in AD by isobaric labeling for relative and absolute quantification, and this finding was further validated by Western blotting and enzyme-linked immunosorbent assay. These data suggest that inflammatory processes, which have been shown to be involved in AD pathology in the brain, are also present in plasma.
引用
收藏
页码:329 / 334
页数:6
相关论文
共 40 条
[11]   8-Plex quantitation of changes in cerebrospinal fluid protein expression in subjects undergoing intravenous immunoglobulin treatment for Alzheimer's disease [J].
Choe, Leila ;
D'Ascenzo, Mark ;
Relkin, Norman R. ;
Pappin, Darryl ;
Ross, Philip ;
Williamson, Brian ;
Guertin, Steven ;
Pribil, Patrick ;
Lee, Kelvin H. .
PROTEOMICS, 2007, 7 (20) :3651-3660
[12]   Identification of oxidized plasma proteins in Alzheimer's disease [J].
Choi, JG ;
Malakowsky, CA ;
Talent, JM ;
Conrad, CC ;
Gracy, RW .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 293 (05) :1566-1570
[13]   Proteomic identification and early validation of complement 1 inhibitor and pigment epithelium -derived factor: Two novel biomarkers of Alzheimer's disease in human plasma [J].
Cutler, Paul ;
Akuffo, Emma L. ;
Bodnar, Wanda M. ;
Briggs, Deborah M. ;
Davis, John B. ;
Debouck, Christine M. ;
Fox, Steven M. ;
Gibson, Rachel A. ;
Gormley, Darren A. ;
Holbrook, Joanna D. ;
Hunter, A. Jacqueline ;
Kinsey, Emma E. ;
Pripffial, Rabinder ;
Richardson, Jill C. ;
Roses, Allen D. ;
Smith, Marjorie A. ;
Sokanas, Nikos ;
Wille, David R. ;
Wu, Wen ;
Yates, John W. ;
Gloger, Israel S. .
PROTEOMICS CLINICAL APPLICATIONS, 2008, 2 (04) :467-477
[14]   Proteome studies of CSF in AD patients [J].
Davidsson, P ;
Sjögren, M .
MECHANISMS OF AGEING AND DEVELOPMENT, 2006, 127 (02) :133-137
[15]   Proteome analysis of cerebrospinal fluid proteins in Alzheimer patients [J].
Davidsson, P ;
Westman-Brinkmalm, A ;
Nilsson, CL ;
Lindbjer, M ;
Paulson, L ;
Andreasen, N ;
Sjögren, M ;
Blennow, K .
NEUROREPORT, 2002, 13 (05) :611-615
[16]   INTERPLAY OF COMPLEMENT AND CYTOKINES IN THE PATHOGENESIS OF SEPTIC SHOCK [J].
DEBOER, JP ;
WOLBINK, GJ ;
THIJS, LG ;
BAARS, JW ;
WAGSTAFF, J ;
HACK, CE .
IMMUNOPHARMACOLOGY, 1992, 24 (02) :135-148
[17]   IMMUNOGLOBULINS AND COMPLEMENT FACTORS IN SENILE PLAQUES - AN IMMUNOPEROXIDASE STUDY [J].
EIKELENBOOM, P ;
STAM, FC .
ACTA NEUROPATHOLOGICA, 1982, 57 (2-3) :239-242
[18]   Plasma Gelsolin is Decreased and Correlates with Rate of Decline in Alzheimer's Disease [J].
Guentert, Andreas ;
Campbell, James ;
Saleem, Muzamil ;
O'Brien, Darragh P. ;
Thompson, Andrew J. ;
Byers, Helen L. ;
Ward, Malcolm A. ;
Lovestone, Simon .
JOURNAL OF ALZHEIMERS DISEASE, 2010, 21 (02) :585-596
[19]   Coagulation and inflammatory markers in Alzheimer's and vascular dementia [J].
Gupta, A ;
Watkins, A ;
Thomas, P ;
Majer, R ;
Habubi, N ;
Morris, G ;
Pansari, K .
INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, 2005, 59 (01) :52-57
[20]   Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study [J].
Hofman, A ;
Ott, A ;
Breteler, MMB ;
Bots, ML ;
Slooter, AJC ;
vanHarskamp, F ;
vanDuijn, CN ;
Van Broeckhoven, C ;
Grobbee, DE .
LANCET, 1997, 349 (9046) :151-154