Cerebrospinal fluid surrounds and supports the central nervous system, including the ventricles and subarachnoid spaces. Cerebrospinal fluid should be an important source of biomarkers for central nervous system diseases because it is in direct contact with the central nervous system. Many studies are reported on cerebrospinal fluid proteomics, highlighting many recent progresses. Here, we review recent advances in proteomics technology and clinical application of cerebrospinal fluid.
Biomarkers ; Cerebrospinal Fluid Proteins ; Proteome ; Proteomics

Alzheimer's disease (AD) is currently diagnosed only via clinical assessments and confirmed by postmortem brain pathology. Biochemical and neuroimaging markers could facilitate diagnosis, predict AD progression from a pre-AD state of mild cognitive impairment (MCI), and be used to monitor efficacies of disease-modifying therapies. It is now clear that cerebrospinal fluid (CSF) levels of A beta 40, A beta 42, total tau and phosphorylated tau have diagnostic values in AD. Measurements of the above CSF markers in combination are useful in predicting the risk of progression from MCI to AD. Recent advances further support a notion that plasma A beta levels, expressed as an A beta 42/A beta 40 ratio, could also be of value. New potential biomarkers are emerging, and CSF or plasma marker profiles may eventually become part of the clinician's toolkit for accurate AD diagnosis and management. These biomarkers, along with clinical assessment, neuropsychological testing and neuroimaging could achieve a much higher diagnostic accuracy for AD and related disorders in the future.
Alzheimer Disease ; blood ; cerebrospinal fluid ; Amyloid beta-Peptides ; blood ; cerebrospinal fluid ; Biomarkers ; blood ; cerebrospinal fluid ; Cognition Disorders ; blood ; cerebrospinal fluid ; Humans ; tau Proteins ; blood ; cerebrospinal fluid

To evaluate the changes of 3', 5'-cyclic adenosine monophosphate (cAMP), thromboxane A2(TXA2) and prostacyclin (PGI2) in cerebrospinal fluid (CSF) in the asphyxiated newborn and explore their roles in hypoxic-ischemic brain damage (HIBD). Thirty-six full term newborns were divided into 3 groups, including 12 with moderate-severe hypoxic-ischaemic encephalopathy (HIE), 13 with mild HIE, 11 without HIE (control group). The levels of cAMP, TXB2 (TXA2 metabolite) and 6-keto-PGF1 alpha (PGI2 metabolite) in CSF and plasma were measured 36-72 h after birth by RIA, and the concentrations were expressed as nM/L (cAMP), ng/L(TXB2 and 6-keto-PGF1 alpha). The infants were followed-up at 6 and 12 month of age and Mental Development Index (MDI) and Psychomotor Development Index (PDI) were measured using Bayley Scales of Infant Development (BSID). The CSF cAMP level in moderate-severe HIE group was 8.60 +/- 2.40, significantly lower than that of the mild HIE group (14.83 +/- 2.84) and the control group (24.43 +/- 2.39) (for both P < 0.01). The levels of TXB2 and 6-keto-PGF1 alpha in CFS in the moderate-severe HIE group (206.06 +/- 29.74, 168.47 +/- 23.02, respectively) were significantly higher than in the mild HIE group (83.37 +/- 28.57, 131.42 +/- 16.57, respectively, P < 0.01) and the control group (41.77 +/- 21.58, 86.23 +/- 13.05, respectively, P < 0.01). The level changes of cAMP, TXB2 and 6-keto-PGF1 alpha in plasma in all groups were similar to those in CSF, but no significant difference was found between mild HIE group and the control group (P > 0.05). The follow-up results showed that MDI and PDI of the moderate-severe HIE group were the lowest (84.79 +/- 13.34, 83.50 +/- 13.28, respectively), followed by mild HIE group (102.19 +/- 7.02, 99.94 +/- 9.08, respectively), with the control group being the highest (116.63 +/- 12.08, 116.69 +/- 10.87, respectively). Univariate analysis showed some significant difference (the moderate-severe HIE group vs. the mild HIE group or the control group, P < 0.01; the mild HIE group vs. the control group P < 0.05). The results suggested that the concentration of cAMP, TXA2 and T/K ratio in CSF after neonatal asphyxia might be sensitive markers in evaluating the severity of brain damage in early stage and predicting the future outcome.
6-Ketoprostaglandin F1 alpha ; cerebrospinal fluid ; Asphyxia Neonatorum ; cerebrospinal fluid ; Biomarkers ; Cyclic AMP ; cerebrospinal fluid ; Epoprostenol ; cerebrospinal fluid ; Female ; Follow-Up Studies ; Humans ; Hypoxia-Ischemia, Brain ; cerebrospinal fluid ; Infant, Newborn ; Male ; Thromboxane A2 ; cerebrospinal fluid ; Thromboxane B2 ; cerebrospinal fluid

Objective To explore the diffusion pattern of tumor markers (TM) from serum to cerebrospinal fluid (CSF) via the blood-brain barrier in patients with elevated serum tumor markers (TM).Methods Inpatients receiving lumbar puncture during hospitalization in our center from January 1, 2013 to December 31, 2015 were divided into study group (n=181) and control group (n=251). The study group consisted of patients with elevated serum TMs but without malignant central nervous system diseases. The control group consisted of patients with normal serum TM levels and without malignant diseases. TMs measured in the study group included elevated serum alpha-fetoprotein (AFP) (n=0), carcinoembryonic antigen (CEA) (n=26), carcinomic antigen(CA)125 (n=39), CA15- 3 (n=3),CA19- 9 (n=19), CA724 (n=47), CYFRA21- 1 (n=49), and SCC (n=17).Levels of TMs in the CSF of study group was compared with that of control group.Results Median CEA (U=0.00,P=0.00),CA19- 9 (U=0.00,P=0.00),CA15- 3 (U=0.00,P=0.04),SCC (U=0.00,P=0.00),CA125 (U=0.00,P=0.00),CA72- 4 (U=3.00,P=0.00)),and CYFRA21- 1 (U=0.00,P=0.00) in CSF were significantly lower than the corresponding serum TM levels in the study group.There was no significant difference between study group and control group for the CSF level of CEA (U=3091.00,P=0.18),CA19- 9 (U=1897.00,P=0.14), CA15- 3 (U=373.50,P=0.91)and SCC (U=1925.50,P=0.76). CSF CA125 (U=2188.00,P=0.00) and CA724 (U=1279.00,P=0.00) levels in the study group were lower than those in control group. CSF level of CYFRA21- 1 (U=1826.50,P=0.00) in study group was higher than that in control group;however, it was still lower than the upper limit of reference value. Conclusion In patients with elevated serum CEA, CA19- 9, CA15- 3, SCC, CA125, and CA72- 4 levels, transblood-brain-barrier diffusion of TMs from serum to CSF is highly unlikely.
Biomarkers, Tumor ; cerebrospinal fluid ; CA-125 Antigen ; cerebrospinal fluid ; CA-19-9 Antigen ; cerebrospinal fluid ; Carcinoembryonic Antigen ; cerebrospinal fluid ; Case-Control Studies ; Central Nervous System Neoplasms ; cerebrospinal fluid ; diagnosis ; Humans ; Mucin-1 ; cerebrospinal fluid ; Reference Values

OBJECTIVETo assess the diagnostic value of tumor markers in the cerebrospinal fluid (CSF) for meningeal carcinomatosis (MC).

METHODSTwenty-one MC patients (including 13 adenocarcinoma and 8 non-adenocarcinoma patients), 72 patients with tuberculous meningitis (TBM) and 23 with primary intracerebral tumors (PIT) were enrolled in this study. Blood and CSF tumor markers including CEA, CA125, CA15-3, CA19-9, CA72-4, CYFRA21-1, AFP and NSE were measured by Roche E170 electrochemiluminescence analyzer and sandwich assay.

RESULTSCSF tumor markers CEA, CA125, CA199 and CYFRA21-1 and the serum tumor markers CEA, CA125, CA153, CA199 and AFP were significantly higher in MC group than in the other two groups. CSF CEA and CA15-3 were significantly higher in adenocarcinoma MC than in non-adenocarcinoma MC patients, but no significant differences were found in the serum tumor markers between the two groups (P>0.05). CSF tumor markers including CEA, CA125, CA15-3, CA72-4 and CYFRA21-1 were positively correlated to the serum tumor markers (P<0.05). CA199 was positively correlated to the disease course (P<0.05), and age was not correlated to any of the indexes (P>0.05).

CONCLUSIONDetection of the tumor markers in the CSF, especially CEA, CA125, CA19-9 and CYFRA21-1, may help in the early diagnosis of MC. CEA and CA15-3 can serve as indicators for differential diagnosis of adenocarcinoma and non-adenocarcinoma.

Adenocarcinoma ; cerebrospinal fluid ; diagnosis ; Adult ; Aged ; Antigens, Neoplasm ; cerebrospinal fluid ; Biomarkers, Tumor ; cerebrospinal fluid ; CA-125 Antigen ; cerebrospinal fluid ; CA-19-9 Antigen ; cerebrospinal fluid ; Carcinoembryonic Antigen ; cerebrospinal fluid ; Female ; Humans ; Keratin-19 ; cerebrospinal fluid ; Male ; Membrane Proteins ; cerebrospinal fluid ; Meningeal Neoplasms ; cerebrospinal fluid ; diagnosis ; Middle Aged ; Young Adult

OBJECTIVETo study the changes of biomarkers in cerebrospinal fluid (CSF) in cerebral amyloid angiopathy (CAA) dementia and Alzheimer(')s disease.

METHODSLevels of amyloid protein β (Aβ42, Aβ40) and phosphorylated Tau-protein (P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011.

RESULTSThe levels of Aβ42, Aβ40, and P-tau in CSF and ratio of Aβ42/Aβ40 were (660.4 ± 265.2) ng/L, (7111.0 ± 1033.4) ng/L, (71.8 ± 51.5) ng/L, and 0.077 ± 0.033, respectively in CAA dementia and (663.6 ± 365.6) ng/L, (5115.0 ± 2931.1) ng/L, (47.7 ± 38.8) ng/L, and 0.192 ± 0.140, respectively in Alzheimer's disease patients. There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers (all P>0.05).

CONCLUSIONMeasurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.

Aged ; Aged, 80 and over ; Amyloid beta-Peptides ; cerebrospinal fluid ; Apolipoproteins E ; genetics ; Biomarkers ; cerebrospinal fluid ; Cerebral Amyloid Angiopathy ; cerebrospinal fluid ; Dementia ; cerebrospinal fluid ; Humans ; Male ; tau Proteins ; cerebrospinal fluid

OBJECTIVETo evaluate the role of brain magnetic resonance imaging (MRI) and tumor markers in the cerebral spinal fluid (CSF) and serum in the diagnosis and treatment of intracranial germinoma in children.

METHODSTotally 5 children (3 girls and 2 boys) who were treated in our hospital between January 2009 and December 2010 due to central diabetes insipidus. All patients received contrast-enhanced brain MRI at presentation and during each follow-up: meanwhile, their anterior pituitary hormones and tumor markers including human chorionic gonadotropin (hCG) and alpha fetoprotein (AFP) were also determined.

RESULTSThree patients presented without prior evaluation, and two patients were referred to our hospital due to exaggerated disease of unknown cause. Their ages at presentation ranged from 8 years to 12 years 1 month, and the duration of symptoms at presentation was between 1 month to 78 months. All of them had polyuria and polydipsia at presentation. Except one child, the other 4 patients had growth retardation and failure in initiation of puberty. Although the growth rate and puberty development were normal during the 2-year follow-up for the excepted child, all child experienced anterior pituitary hypofunction and an increased concentration of plasma prolactin after the lesion became enlarged. Three patients had cerebral hernia, which presented in 18, 24, and 78 months, respectively. In three patients, brain MRI at presentation showed isolated pituitary stalk thickening, which further developed into massive tumor in the hypothalamus pituitary region 18-22 months later; in the remaining two patients, large brain tumor was found via MRI at their first presentations. In all five patients, the posterior pituitary gland (bright spot) disappeared on T1-weighted MRI images. CSF hCG elevated in all five patients, and serum hCG increased in four patients; the level of hCG varied with the mass size of tumor. Serum and CSF AFP increased in only one patient.

CONCLUSIONSPatients with idiopathic central diabetes insipidus must be closely followed to identify the etiology, especially when anterior pituitary hormone deficiencies are detected. For patients with normal brain MRI results or simply isolated pituitary stalk thickening at presentation, the changes of serial contrast-enhanced brain MRI should be observed during follow-up to ensure the early detection of an evolving occult hypothalamic-stalk lesion. Determination of CSF hCG at the first presentation may be useful, because an increased CSF level of hCG precedes MRI abnormalities.

Biomarkers, Tumor ; analysis ; blood ; cerebrospinal fluid ; Brain Neoplasms ; blood ; cerebrospinal fluid ; diagnosis ; Child ; Female ; Germinoma ; blood ; cerebrospinal fluid ; diagnosis ; Humans ; Magnetic Resonance Imaging ; Male ; Retrospective Studies

Idiopathic Normal Pressure Hydrocephalus (NPH) is a debilitating condition of the elderly. The patient is typically "wet, wobbly and wonky", to different degrees of the triad. The diagnosis is supported by the radiologic finding of dilated ventricles, determined by an elevated Evan's Index (EI) without a demonstrable cause. Patients with newly diagnosed NPH typically respond to ventriculo-peritoneal shunting (VPS). NPH-related dementia is possibly the only surgically reversible dementia. An elevated cerebrospinal fluid (CSF) fl ow rate (FR) is associated with a positive response to shunting. However, post-shunting EI and FRs are unpredictable. Of late, intracranial apparent diffusion coefficient (ADC) quantification via Diffusion Weighted Imaging (DWI) has been emerging as a possible marker in NPH diagnosis. A local study, conducted on a national level, to study the relationship of EI, FR and ADC to pre- and post-shunt clinical measurements has just ended. This review seeks to reconcile the current thinking of NPH, magnetic resonance imaging (MRI) quantification and clinical evaluation, and in the process shed some light on major pathophysiological determinants of the disease.
Biomarkers ; cerebrospinal fluid ; Cerebrospinal Fluid ; physiology ; secretion ; Diffusion Magnetic Resonance Imaging ; Humans ; Hydrocephalus, Normal Pressure ; diagnosis ; physiopathology

This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment (VCI) with the goal of providing a target for the treatment and prevention of VCI. Inpatients with proven cerebral infarction on cranial computed tomography (CT) were recruited as the ischemic cerebrovascular diseases (ICVD) group, and the patients with mixed stroke were excluded. In ICVD group, 12 patients were diagnosed as having VCI and served as VCI group. Inpatients undergoing surgical operation in our hospital were enrolled as control group. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was employed to detect the levels of hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid of patients with ICVD. Associations between the levels of these factors and the Mini-Mental State Examination (MMSE) score were evaluated. In ICVD and VCI groups, the levels of HIF-1α and NGF in the cerebrospinal fluid were markedly lower than those in control group (P=0.037 and P=0.000; P=0.023 and P=0.005). In ICVD and VCI groups, the MMSE score was negatively related to VEGF level in the cerebrospinal fluid (r=-0.327, P=0.021; r=-0.585, P=0.046). In VCI group, HIF-1α level was correlated with NGF level (r=0.589, P=0.044). HIF-1α and NGF are involved in ischemic and hypoxic cerebral injury. The HIF signaling pathway plays an important role in intrinsic neuroprotection. Upregulation and maintenance of HIF-1α and NGF expression may attenuate VCI. Changes in VEGF levels are related to the occurrence and development of cognitive impairment.
Biomarkers ; cerebrospinal fluid ; Brain-Derived Neurotrophic Factor ; cerebrospinal fluid ; Cerebral Infarction ; cerebrospinal fluid ; complications ; diagnosis ; Cognition Disorders ; cerebrospinal fluid ; complications ; diagnosis ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; cerebrospinal fluid ; Male ; Middle Aged ; Nerve Growth Factor ; cerebrospinal fluid ; Reproducibility of Results ; Sensitivity and Specificity ; Vascular Endothelial Growth Factor A ; cerebrospinal fluid

OBJECTIVETo study the expression of B-cell activating factor (BAFF) in the serum and cerebrospinal fluid of patients with neuromyelitis optical (NMO).

METHODSClinical data were collected from 44 patients with NMO and 38 patients with multiple sclerosis (MS). Thirty healthy controls and 15 controls with noninflammatory neurological diseases were also recruited. The concentration of BAFF in the serum and cerebrospinal fluid were measured by enzyme-linked immunosorbent assay (ELISA).

RESULTSThe mean serum BAFF level was 250.2 ± 126.9 pg/ml in NMO patients, 249.6 ± 130.7 pg/ml in MS patients, and 222.9 ± 126.1 pg/ml in the control subjects, showing no significant difference among the 3 groups (P>0.05). The mean BAFF level in the CSF was significantly higher in NMO patients than in MS patients (525.8 ± 230.0 pg/ml vs 298.4 ± 141.9 pg/ml, P<0.05), and higher in MS patients than in the control subjects (141.4 ± 76.2 pg/ml, P<0.05). Both NMO and MS group showed a positive correlation between EDSS scores and CSF BAFF level. But in NMO patients, CSF BAFF level was not associated with AQP4-antibody titer.

CONCLUSIONBAFF in the CSF may be a useful biomarker for a differential diagnosis of NMO from MS and has an important value in evaluating the disease severity.

B-Cell Activating Factor ; blood ; cerebrospinal fluid ; Biomarkers ; blood ; cerebrospinal fluid ; Case-Control Studies ; Diagnosis, Differential ; Enzyme-Linked Immunosorbent Assay ; Humans ; Multiple Sclerosis ; blood ; cerebrospinal fluid ; Neuromyelitis Optica ; blood ; cerebrospinal fluid