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

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

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

There are many diseases that have a characteristic protein electrophoretic patterns of serum and cerebrospinal fluid. The protein electrophoretic study of serum and cerebrospinal fluid has been used clinically for the diagnosis of such diseases. There are very few studies and references on this subject to available in Korea. Therefore authors studied the protein electrophoretic patterns of serum and cerebrospinal fluid in 20 cases of full term infants and 20 cases of premature infants by using the cellulose acetate method delivered in Hanyang University Hospital during the period of 6 months from March 1980 to August 1980. The results obtained were as follows: 1. In electrophoretic pattern of cerebrospinalfluid protein, there was a prealbumin zone which was the rapidly migrating fraction of albumin and it was specific to cerebrospinal fluid. 2. Serum total proteins in full term infants were 5. 9+/-0. 7 gm/dl, and the percentage composition of proteins were albumin 55.2+/-6.5%, a1-globulin 3.2+/-0.7%, a2-globulin 7.2+/-1.4%, b-globulin 15.1?.1% and r-globulin 19.4+/-4. 8%. 3. Serum total proteins in premature infants were 5. 6+/-.1.0gm/dl, and the percentage cornposition of proteins were albumin 56.0+/-4.1%, a1 -globulin 3. 5+/-0.5%, a2-globulin 7.9+/-0.8%, b-globulin 16.7+/-5.3%, and r-globulin 15.9+/-4.8%. 4. CSF total proteins in full term infants were 104.0+/-21.3mg/dl, and the percentage composition of proteins were prealbumin 2.2+/-1.1%, albumin 67.4+/-6.3%, a1-globulin 3.9+/-1.1 a2 -globulin 4.9+/-2.8%, b-globulin 12.5+/-1.2%, and r-globulin 9.0+/-3.6%. 5. CSF total proteins in premature infants were 151.1+/-65.2mg/dl, and the percentage composition of proteins were prealbumin 2.2+/-0.5%, albumin 71.9+/-0.8%, a1-globulin 3.1+/-1.0%, a1-globulin 4.7+/-1.9%, B-globulin 9.4+/-2.4%, and r-globulin 8.5+/-2.1%. 6. CSF to serum proteins ratio and CSF to serum albumin ratio x 1,000 were 1/57 and 22.1+/-6.4 in full term infants, and 1/37 and 35.5+/-10.3 in premature infants, respectively.
Blood Proteins ; Cellulose ; Cerebrospinal Fluid Proteins* ; Cerebrospinal Fluid* ; Diagnosis ; Electrophoresis ; Humans ; Infant ; Infant, Newborn* ; Infant, Premature ; Korea ; Prealbumin ; Serum Albumin

OBJECTIVETo explore the role of S100B protein in the early diagnosis, treatment, and prognosis judgement of craniocerebral injury.

METHODSIn this study, we reviewed the domestic and foreign research reports about the relationship between S100B protein and craniocerebral injury.

RESULTSThe concentration of S100B protein had a different increase based on the degree of injury in early stage after craniocerebral injury, and the increasing degree of S100B protein showed a positive correlation with the grading of pathogenetic condition and prognosis of craniocerebral injury.

CONCLUSIONSS100B protein may be taken as a specific index of early diagnosis, grading of pathogenetic condition, and prognosis judgement after craniocerebral injury. To grasp and regulate the mechanism of neurotoxicity and to elucidate the therapeutic effect of S100B protein will be a research direction in clinical treatment of craniocerebral injury.

Craniocerebral Trauma ; cerebrospinal fluid ; diagnosis ; Humans ; Nerve Growth Factors ; cerebrospinal fluid ; Prognosis ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins ; cerebrospinal fluid

OBJECTIVEBacterial meningitis is a kind of central nervous system infection with a high incidence, disability and fatality in children. Prompt diagnosis and treatment are associated with an improved prognosis. Low positive rate of bacterial cultures of the cerebrospinal fluid (CSF) makes it difficult to make a definite diagnosis. This experiment aimed to investigate a proteome profile of normal CSF of Chinese children by two-dimensional polyacrydamide gel electrophoresis (2-DE), and to sieve the disease-specific proteins of Staphylococcus epidermidis meningitis (SeM) to provide basis for early diagnosis and treatment of SeM.

METHODSFour mL CSF samples were obtained respectively from SeM and normal children. The separated proteins with immobile pH gradient (IPG) 2-DE technology and protein spots were visualized by Coomassie Brilliant Blue staining. The stained 2-DE gels were scanned on the Imagescanner and pictures were obtained through Labscan software. The images were analyzed with PDQuest software and the differences of protein spots were compared between the SeM and normal children.

RESULTSMean protein spots of the 2-DE gels were 438 and 425 in the SeM and normal groups respectively. Twenty-five protein spots only occurred in normal CSF and 12 spots only occurred in the SeM group. The expression of 6 protein spots showed up-regulation and that of 19 showed down-regulation in the SeM group compared with that in the normal group.

CONCLUSIONSA 2-DE profile of CSF proteome was successfully established in SeM and normal children through proteomic technique. By the differentiated analysis of these CSF 2-DE gels, the differences of CSF proteome profiles were found between SeM and normal children. Future analysis and identification of these spots will contribute to find out the disease specific proteins of SeM and to provide basis for early diagnosis and therapy of this disorder.

Cerebrospinal Fluid Proteins ; analysis ; Child ; Humans ; Meningitis, Bacterial ; cerebrospinal fluid ; Pilot Projects ; Proteomics ; Reagent Kits, Diagnostic ; Staphylococcal Infections ; cerebrospinal fluid ; Staphylococcus epidermidis

Cataplexy is one of the most pathognomonic symptoms in narcolepsy. This study was designed to investigate the frequency of the HLA-DQB1 allele and cerebrospinal fluid (CSF) hypocretin levels in Korean narcoleptics with cataplexy as compared with those who do not have cataplexy. Seventy-two narcoleptics were selected based on polysomnography and multiple sleep latency test as well as their history and clinical symptoms at Sleep Disorders Clinic. The patients were divided into a narcolepsy with cataplexy group (n=56) and a narcolepsy without cataplexy group (n=16). All patients were subjected to HLA typing to determine the frequency of DQB1 allele and to spinal tapping to measure the level of CSF hypocretin. In cataplexy-positive patients, as compared with cataplexy-negative patients, the frequency of HLA-DQB1*0602 was found to be significantly high (89.3% vs. 50.0%) (p=0.003). On the other hand, the frequency of HLA-DQB1*0601 was found to be significantly low (0% vs. 43.8%) (p<0.001). In 48 of 56 cataplexy-positive patients (85.7 %), hypocretin levels were decreased (< or =110 pg/mL). However, only 6 of 16 cataplexy-negative patients (37.5%) exhibited a decreased hyopcretin level (p<0.001). The high frequency of HLA-DQB1*0602, low frequency of HLA-DQB1*0601 and low hypocretin levels in cataplexy-positive groups suggest that cataplexy-positive narcolepsy might be an etiologically different disease entity from the cataplexy-negative.
Sleep, REM ; Neuropeptides/*cerebrospinal fluid ; Narcolepsy/cerebrospinal fluid/*genetics ; Middle Aged ; Male ; Intracellular Signaling Peptides and Proteins/*cerebrospinal fluid ; Humans ; HLA-DQ Antigens/*genetics ; Female ; Child ; Cataplexy/cerebrospinal fluid/*genetics ; *Alleles ; Aged ; Adult ; Adolescent

Human genetic prion diseases (gPrDs) are directly associated with mutations and insertions in the PRNP (Prion Protein) gene. We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and June 2020. Nineteen different subtypes were identified and gPrDs accounted for 10.9% of all diagnosed PrDs within the same period. Some subtypes of gPrDs showed a degree of geographic association. The age at onset of Chinese gPrDs peaked in the 50-59 year group. Gerstmann-Sträussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI) cases usually displayed clinical symptoms earlier than genetic Creutzfeldt-Jakob disease (gCJD) patients with point mutations. A family history was more frequently recalled in P105L GSS and D178N FFI patients than T188K and E200K patients. None of the E196A gCJD patients reported a family history. The gCJD cases with point mutations always developed clinical manifestations typical of sporadic CJD (sCJD). EEG examination was not sensitive for gPrDs. sCJD-associated abnormalities on MRI were found in high proportions of GSS and gCJD patients. CSF 14-3-3 positivity was frequently detected in gCJD patients. Increased CSF tau was found in more than half of FFI and T188K gCJD cases, and an even higher proportion of E196A and E200K gCJD patients. 63.6% of P105L GSS cases showed a positive reaction in cerebrospinal fluid RT-QuIC. GSS and FFI cases had longer durations than most subtypes of gCJD. This is one of the largest studies of gPrDs in East Asians, and the illness profile of Chinese gPrDs is clearly distinct. Extremely high proportions of T188K and E196A occur among Chinese gPrDs; these mutations are rarely reported in Caucasians and Japanese.
14-3-3 Proteins/cerebrospinal fluid* ; China ; Creutzfeldt-Jakob Syndrome/genetics* ; Humans ; Mutation/genetics* ; Prion Diseases/genetics* ; Prion Proteins/genetics* ; Prions/genetics* ; tau Proteins/cerebrospinal fluid*

Alzheimer's disease (AD), also called presenile dementia, is one of the most common neurodegenerative diseases in elderly people. The main pathological features of AD include senile plaques (SPs), neurofibrillary tangles (NFTs) and neuron loss. A biomarker is a characteristic that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Class biomarkers of AD such as Abeta and phosphorylated tau have been widely used in clinical diagnosis of AD patients. Recently, novel technologies like proteomics, genomics, and imaging techniques have expanded the role of a biomarker from early diagnosis to monitoring the progression of diseases and evaluating the response to various treatments. In this article, we will review the progress of various biomarkers of AD.
Adipokines ; cerebrospinal fluid ; Alzheimer Disease ; cerebrospinal fluid ; diagnosis ; diagnostic imaging ; metabolism ; Amyloid beta-Peptides ; cerebrospinal fluid ; Biomarkers ; analysis ; Chitinase-3-Like Protein 1 ; Fluorodeoxyglucose F18 ; Humans ; Lectins ; cerebrospinal fluid ; Peptide Fragments ; cerebrospinal fluid ; Phosphorylation ; Positron-Emission Tomography ; Presenilins ; analysis ; alpha 1-Antitrypsin ; blood ; tau Proteins ; cerebrospinal fluid