Epidemiological and molecular studies suggest that Alzheimer’s disease (AD) has multiple etiologies including genetic mutations, genetic variations affecting susceptibility and environmental factors. These aspects can promote the formation and accumulation of insoluble amyloid-β and hyperphosphorylated tau. Since the disease is multifactorial and clinical diagnosis is highly exclusive, the need for a sensitive, specific and reliable biomarker is crucial.
The concept of a biomarker implies sensitivity and specificity relative to the condition being considered. For clinical practice, AD diagnosis has been based on adherence to clinical criteria such as the NINCDS/ADRDA and DSM-IV. A more recent set of diagnostic criteria proposed incorporates imaging findings into the diagnosis of AD.
In this article, we consider the most studied candidates or group of candidates for AD biomarkers, including pathological processes and proteins (amyloid-β, tau, oxidative stress, mitochondrial/metabolic changes and cell-cycle processes), or autoantibodies thereto, as well as genetic factors.
Biomarkers in Alzheimer’s disease: past, present and future
Katarzyna Gustaw-Rothenberg1,2, Alan Lerner1, David J Bonda3, Hyoung-gon Lee3, Xiongwei Zhu3, George Perry3,4 & Mark A Smith3††Author for correspondence
Biomarkers in Medicine
February 2010, Vol. 4, No. 1, Pages 15-26
Showing posts with label biomarker. Show all posts
Showing posts with label biomarker. Show all posts
Thursday
Preoperative serum placenta growth factor level is a prognostic biomarker in colorectal cancer
PURPOSE: Increased angiogenesis at the site of the primary tumor in colorectal cancer has been associated with poor prognosis and relapse of disease. We previously demonstrated that the tissue level of placenta growth factor expression was upregulated in colorectal cancer and correlated with disease progression and patient survival. The aims of this study are to examine the prognostic value of serum placenta growth factor, vascular endothelial growth factor, and sFlt-1 and to compare them with the carcinoembryonic antigen levels in patients with colorectal cancer.
METHODS: Preoperative serum from 86 patients and serum from 30 healthy controls was included. The levels of sFlt-1, placenta growth factor, vascular endothelial growth factor in the serum were assayed and correlated with the clinical stage results.
RESULTS: Serum placenta growth factor, but not vascular endothelial growth factor, increased; sFlt-1 decreased in patients with preoperative colorectal cancer, compared with healthy controls. Higher preoperation serum placenta growth factor levels were associated with higher risk of recurrence. Preoperation serum placenta growth factor, but not carcinoembryonic antigen, was a prognostic indicator in patients with Stage III colorectal cancer. When we use the median level (20.6 pg/ml) of preoperative serum placenta growth factor as a cutoff point, the sensitivity, specificity, and positive predictive value for tumor recurrence and survival was 80, 54, 80% and 70, 56, 70%, respectively.
CONCLUSIONS: Preoperative serum placenta growth factor levels were higher in patients with colorectal cancer, were negatively correlated with the serum sFlt-1, and could be used as a prognostic indicator for recurrence and survival for colorectal cancer.
Wei SC, Liang JT, Tsao PN, Hsieh FJ, Yu SC, Wong JM.
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
METHODS: Preoperative serum from 86 patients and serum from 30 healthy controls was included. The levels of sFlt-1, placenta growth factor, vascular endothelial growth factor in the serum were assayed and correlated with the clinical stage results.
RESULTS: Serum placenta growth factor, but not vascular endothelial growth factor, increased; sFlt-1 decreased in patients with preoperative colorectal cancer, compared with healthy controls. Higher preoperation serum placenta growth factor levels were associated with higher risk of recurrence. Preoperation serum placenta growth factor, but not carcinoembryonic antigen, was a prognostic indicator in patients with Stage III colorectal cancer. When we use the median level (20.6 pg/ml) of preoperative serum placenta growth factor as a cutoff point, the sensitivity, specificity, and positive predictive value for tumor recurrence and survival was 80, 54, 80% and 70, 56, 70%, respectively.
CONCLUSIONS: Preoperative serum placenta growth factor levels were higher in patients with colorectal cancer, were negatively correlated with the serum sFlt-1, and could be used as a prognostic indicator for recurrence and survival for colorectal cancer.
Wei SC, Liang JT, Tsao PN, Hsieh FJ, Yu SC, Wong JM.
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Sunday
Depletion of one, six, twelve or twenty major blood proteins before proteomic analysis:
Depletion of major blood proteins is one of the most promising approaches to access low abundant biomarkers using proteomics. Immunocapture columns often used for this purpose exist in different formats depending on the number of major proteins removed. In this article, we compared the relative interest of depleting either one (albumin), six (albumin, IgG, IgA, transferrin, alpha1-antitrypsin, and haptoglobin), twelve (the previous six and apo A-I and -II, orosomucoid, alpha2-macroglobulin, fibrinogen, IgM) or twenty blood proteins (the previous twelve and IgD, ceruloplasmin, apo B, complement C1q, C3, C4, plasminogen, and prealbumin). Such study raises interesting issues related to the reproducibility, practicability, specificity of the immunocapture, and to the impact of removing not only the selected molecules, but also associated peptides and proteins. Depleted sera were here analysed using different proteomic approaches, including two dimensional electrophoresis and SELDI-TOF. Altogether, our results clearly confirmed the interest of depleting major blood proteins for the proteomic detection of low abundant components. However, we observed that increasing the number of depleted proteins from twelve to twenty had a limited beneficial impact and might increase drawbacks in removing associated peptides and proteins. This conclusion is however related to the technologies that we have used, and we believe that it is necessary to adapt the immunocapture to the analytical method employed, and to the ratio between wanted and unwanted proteins removed.
Roche S, Tiers L, Provansal M, Seveno M, Piva MT, Jouin P, Lehmann S.
CHU Montpellier, Biochimie Saint Eloi, Plateforme de Protéomique Clinique 80 av A. Fliche, 34295 Montpellier Cedex 5, France; Institut de Génétique Humaine du CNRS, 141 rue de la Cardonille, 34396 Montpellier, France.
Roche S, Tiers L, Provansal M, Seveno M, Piva MT, Jouin P, Lehmann S.
CHU Montpellier, Biochimie Saint Eloi, Plateforme de Protéomique Clinique 80 av A. Fliche, 34295 Montpellier Cedex 5, France; Institut de Génétique Humaine du CNRS, 141 rue de la Cardonille, 34396 Montpellier, France.
Wednesday
Cystatin C in cerebrospinal fluid as a biomarker of ALS.
Department of Neurology, Graduate School of Medicine, Hokkaido University, Sapporo City, Hokkaido, Japan. tujitti@jb3.so-net.ne.jp
Amyotrophic lateral sclerosis (ALS) is diagnosed on the basis of progressive symptoms in both the upper and lower motor neurons. Because there are no specific biomarkers for ALS, it is difficult to diagnose this disease in its early stages. Cerebrospinal fluid (CSF) samples were obtained from 14 patients in the early stages of ALS, from 13 with polyneuropathy, and from 16 with other neurological disorders. The concentration of cystatin C in the CSF was measured using a sandwich enzyme-linked immunosorbent assay (ELISA) kit. The concentration of cystatin C in the CSF was significantly lower in ALS patients than in the control subjects who were patients with polyneuropathy or other neurological diseases (patients with ALS, polyneuropathy, and other diseases exhibited 5.5 +/- 0.3, 6.7 +/- 0.4, and 6.9 +/- 0.3 mg/L cystatin C, respectively; ALS patients vs. control subjects: p = 0.014 and ALS patients vs. polyneuropathy patients: p = 0.024). Cystatin C may be a useful biomarker of ALS and can be used to distinguish between ALS and polyneuropathy.
Amyotrophic lateral sclerosis (ALS) is diagnosed on the basis of progressive symptoms in both the upper and lower motor neurons. Because there are no specific biomarkers for ALS, it is difficult to diagnose this disease in its early stages. Cerebrospinal fluid (CSF) samples were obtained from 14 patients in the early stages of ALS, from 13 with polyneuropathy, and from 16 with other neurological disorders. The concentration of cystatin C in the CSF was measured using a sandwich enzyme-linked immunosorbent assay (ELISA) kit. The concentration of cystatin C in the CSF was significantly lower in ALS patients than in the control subjects who were patients with polyneuropathy or other neurological diseases (patients with ALS, polyneuropathy, and other diseases exhibited 5.5 +/- 0.3, 6.7 +/- 0.4, and 6.9 +/- 0.3 mg/L cystatin C, respectively; ALS patients vs. control subjects: p = 0.014 and ALS patients vs. polyneuropathy patients: p = 0.024). Cystatin C may be a useful biomarker of ALS and can be used to distinguish between ALS and polyneuropathy.
Evaluation of the DNA Damaging Potential of Cannabis Cigarette Smoke
United Kingdom, Department of Biosciences and Nutrition, Unit of Molecular Epidemiology, Karolinska Institute, S-141 57 Huddinge, Sweden, and Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine, University of Leicester, Fifth Floor RKCSB, Leicester Royal Infirmary, Leicester, LE2 7LX United Kingdom.
Acetaldehyde is an ubiquitous genotoxic compound that has been classified as a possible carcinogen to humans. It can react with DNA to form primarily a Schiff base N(2)-ethylidene-2'-deoxyguanosine (N(2)-ethylidene-dG) adduct. An online column-switching valve liquid chromatography tandem mass spectrometry (LC-MS/MS) selected reaction monitoring (SRM) method was developed for the determination of N(2)-ethylidene-dG adducts in DNA following reduction with sodium cyanoborohydride (NaBH(3)CN) to the chemically stable N(2)-ethyl-2'-deoxyguanosine (N(2)-ethyl-dG) adduct. Accurate quantitation of the adduct was obtained by the addition of the [(15)N(5)]N(2)-ethyl-dG stable isotope-labeled internal standard prior to enzymatic hydrolysis of the DNA samples to 2'-deoxynucleosides with the incorporation of NaBH(3)CN in the DNA hydrolysis buffer.
The method required 50 mug of hydrolyzed DNA on column for the analysis, and the limit of detection for N(2)-ethyl-dG was 2.0 fmol. The analysis of calf thymus DNA treated in vitro with acetaldehyde (ranging from 0.5 to 100 mM) or with the smoke generated from 1, 5, and 10 cannabis cigarettes showed linear dose-dependent increases in the level of N(2)-ethyl-dG adducts (r = 0.954 and r = 0.999, respectively). Similar levels (332.8 +/- 21.9 vs 348.4 +/- 19.1 adducts per 10(8) 2'-deoxynucleosides) of N(2)-ethyl-dG adducts were detected following the exposure of calf thymus DNA to 10 tobacco or 10 cannabis cigarettes.
No significant difference was found in the levels of N(2)-ethyl-dG adducts in human lung DNA obtained from nonsmokers (n = 4) and smokers (n = 4) with the average level observed as 13.3 +/- 0.7 adducts per 10(8) 2'-deoxynucleosides. No N(2)-ethyl-dG adducts were detected in any of the DNA samples following analysis with the omission of NaBH(3)CN from the DNA hydrolysis buffer. In conclusion, these results provide evidence for the DNA damaging potential of cannabis smoke, implying that the consumption of cannabis cigarettes may be detrimental to human health with the possibility to initiate cancer development.
Acetaldehyde is an ubiquitous genotoxic compound that has been classified as a possible carcinogen to humans. It can react with DNA to form primarily a Schiff base N(2)-ethylidene-2'-deoxyguanosine (N(2)-ethylidene-dG) adduct. An online column-switching valve liquid chromatography tandem mass spectrometry (LC-MS/MS) selected reaction monitoring (SRM) method was developed for the determination of N(2)-ethylidene-dG adducts in DNA following reduction with sodium cyanoborohydride (NaBH(3)CN) to the chemically stable N(2)-ethyl-2'-deoxyguanosine (N(2)-ethyl-dG) adduct. Accurate quantitation of the adduct was obtained by the addition of the [(15)N(5)]N(2)-ethyl-dG stable isotope-labeled internal standard prior to enzymatic hydrolysis of the DNA samples to 2'-deoxynucleosides with the incorporation of NaBH(3)CN in the DNA hydrolysis buffer.
The method required 50 mug of hydrolyzed DNA on column for the analysis, and the limit of detection for N(2)-ethyl-dG was 2.0 fmol. The analysis of calf thymus DNA treated in vitro with acetaldehyde (ranging from 0.5 to 100 mM) or with the smoke generated from 1, 5, and 10 cannabis cigarettes showed linear dose-dependent increases in the level of N(2)-ethyl-dG adducts (r = 0.954 and r = 0.999, respectively). Similar levels (332.8 +/- 21.9 vs 348.4 +/- 19.1 adducts per 10(8) 2'-deoxynucleosides) of N(2)-ethyl-dG adducts were detected following the exposure of calf thymus DNA to 10 tobacco or 10 cannabis cigarettes.
No significant difference was found in the levels of N(2)-ethyl-dG adducts in human lung DNA obtained from nonsmokers (n = 4) and smokers (n = 4) with the average level observed as 13.3 +/- 0.7 adducts per 10(8) 2'-deoxynucleosides. No N(2)-ethyl-dG adducts were detected in any of the DNA samples following analysis with the omission of NaBH(3)CN from the DNA hydrolysis buffer. In conclusion, these results provide evidence for the DNA damaging potential of cannabis smoke, implying that the consumption of cannabis cigarettes may be detrimental to human health with the possibility to initiate cancer development.
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