Analysis of potential diagnostic biomarkers in cerebrospinal fluid of idiopathic normal pressure hydrocephalus by proteomics.
BACKGROUND
The pathogenesis of idiopathic normal pressure hydrocephalus (INPH) is unknown, and the syndrome of INPH remains a diagnostic and therapeutic challenge. The present study investigated the disease-specific proteins that aid in the diagnosis and treatment of INPH and thus to study their role in the disease process.


METHODS
A comparative proteomic analysis was used for clinical screening of cerebrospinal fluid (CSF) proteins in 15 patients with INPH and compared with 12 normal subjects. Furthermore, enzyme linked immunosorbent assay (ELISA) was performed for comparison with CSF proteins between individual INPH patients and controls.


RESULTS
Seven proteins and their isoforms, including leucine-rich alpha-2-glycoprotein (LRG), alpha1-antichymotrypsin, apolipoprotein D, apolipoprotein J, haptoglobin alpha1, serum albumin, and alpha-1-microglobulin/bikunin precursor showed significant changes in CSF of INPH patients compared with controls by proteomic analysis. And significant higher CSF levels of LRG in INPH patients compared with controls were found by ELISA.


CONCLUSIONS
These results indicate that there are significant differences in the expression of certain proteins in the CSF of patients with INPH and normal subjects. In particular, the CSF level assay of LRG suggests that LRG is a specific biomarker for INPH and has potential use in the diagnosis and indication for CSF shunting.
Li
X
X
Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan. lixf72@hotmail.com
Miyajima
M
M
Mineki
R
R
Taka
H
H
Murayama
K
K
Arai
H
H
D000368:Aged; D000510:Alpha-Globulins / Q000032:analysis / Q000134:cerebrospinal fluid; D001053:Apolipoproteins / Q000032:analysis / Q000134:cerebrospinal fluid; D053399:Apolipoproteins D; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000378:metabolism*; D051152:Clusterin / Q000032:analysis / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000032:analysis / Q000134:cerebrospinal fluid; D006242:Haptoglobins / Q000032:analysis / Q000134:cerebrospinal fluid; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000503:physiopathology; D008297:Male; D026901:Membrane Transport Proteins / Q000032:analysis / Q000134:cerebrospinal fluid; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid*; D011237:Predictive Value of Tests; D040901:Proteomics / Q000379:methods*; D012709:Serum Albumin / Q000032:analysis / Q000134:cerebrospinal fluid; D015854:Up-Regulation / Q000502:physiology; D000514:alpha 1-Antichymotrypsin / Q000032:analysis / Q000134:cerebrospinal fluid
C024328:APOD protein, human; D000510:Alpha-Globulins; D001053:Apolipoproteins; D053399:Apolipoproteins D; D015415:Biomarkers; C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; C485359:HP protein, human; D006242:Haptoglobins; C015246:LRG1 protein, human; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012709:Serum Albumin; D000514:alpha 1-Antichymotrypsin; C016001:alpha-1-microglobulin