ABSTRACT
Cerebral and extracerebral cholesterol metabolism are altered in Alzheimer's disease (AD) as indicated by reduced plasma levels of the cholesterol elimination products 24S-hydroxycholesterol, which is of cerebral origin, and of 27-hydroxycholesterol, which is formed extracerebrally. However, it has to be evaluated, if changes of cholesterol metabolism in the whole body or in the CNS are exclusively due to the altered elimination of cholesterol or are also due to altered de novo synthesis in AD. We investigated CSF and plasma levels of cholesterol and of its precursors lanosterol, lathosterol and desmosterol in AD patients and non-demented controls. We found CSF levels of cholesterol (p=0.011), absolute levels of all investigated cholesterol precursors (each p<0.001) and ratios of cholesterol precursors/cholesterol (each <0.01) to be lower in AD patients as compared to controls. In plasma, the absolute levels of lanosterol (p=0.026) and lathosterol (p<0.001) and the ratio of lathosterol/cholesterol (p=0.002) but none of the other investigated parameters were reduced in AD patients (p>0.1). Furthermore, ratios of desmosterol/lathosterol in CSF (p=0.023) and plasma (p=0.009) were higher in AD patients as compared to controls. Our data support the hypothesis that cholesterol metabolism is altered in AD and further suggest that especially cholesterol de novo synthesis within the CNS of AD patients might be reduced. These findings raise doubt on a beneficial effect of cholesterol lowering treatment in manifest AD.
Subject(s)
Alzheimer Disease/metabolism , Cholesterol/metabolism , Lanosterol/metabolism , Aged , Aged, 80 and over , Alleles , Alzheimer Disease/blood , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/genetics , Apolipoprotein E4/genetics , Case-Control Studies , Cholesterol/blood , Cholesterol/cerebrospinal fluid , Desmosterol/blood , Desmosterol/cerebrospinal fluid , Desmosterol/metabolism , Female , Gene Frequency , Humans , Lanosterol/blood , Lanosterol/cerebrospinal fluid , Male , Middle Aged , Models, BiologicalABSTRACT
The concept of tumor markers was reviewed, and the potential uses of markers of central nervous system (CNS) tumors and methods for their evaluation were discussed. Markers examined included lactate dehydrogenase, aspartate aminotransferase, fructose-bisphosphate aldolase, the polyamines, desmosterol, and several other enzymatic, nonenzymatic, and immunologic markers. Data collated from the clinical studies surveyed showed isocitrate dehydrogenase, desmosterol, and the polyamines to have the greatest potential utility in the diagnosis of CNS tumors.
Subject(s)
Brain Neoplasms/cerebrospinal fluid , Antigens, Neoplasm/cerebrospinal fluid , Aspartate Aminotransferases/cerebrospinal fluid , Brain Neoplasms/diagnosis , Brain Neoplasms/therapy , Desmosterol/cerebrospinal fluid , Fructose-Bisphosphate Aldolase/cerebrospinal fluid , Humans , L-Lactate Dehydrogenase/cerebrospinal fluid , Polyamines/cerebrospinal fluid , Research DesignABSTRACT
In clinical practice, the examination of cerebrospinal fluid from patients with primary or metastatic brain tumors is commonly limited to cytomorphologic and routine chemistry analysis. The relative lack of sensitivity and specificity of these tests has led to a search for markers that can detect nervous system involvement by neoplasms at an earlier stage and even predict the site of origin of the neoplasms. This article summarizes recent investigators of biochemical tumor markers and cytoplasmic and cell surface markers in cerebrospinal fluid from patients with nervous system tumors.
Subject(s)
Brain Neoplasms/cerebrospinal fluid , Antibodies, Monoclonal , Antibodies, Neoplasm , Antigens, Neoplasm/analysis , Brain Neoplasms/immunology , Brain Neoplasms/secondary , Carcinoembryonic Antigen/analysis , Chorionic Gonadotropin/cerebrospinal fluid , Chorionic Gonadotropin, beta Subunit, Human , Desmosterol/cerebrospinal fluid , Glial Fibrillary Acidic Protein/cerebrospinal fluid , Glucuronidase/cerebrospinal fluid , Humans , Immunoglobulins/cerebrospinal fluid , L-Lactate Dehydrogenase/cerebrospinal fluid , Lymphocytes/classification , Neoplasm Proteins/cerebrospinal fluid , Peptide Fragments/cerebrospinal fluid , Pituitary Hormones/cerebrospinal fluid , Polyamines/cerebrospinal fluid , alpha-Fetoproteins/cerebrospinal fluid , beta 2-Microglobulin/cerebrospinal fluidABSTRACT
Biological markers of tumors are compounds or enzymatic activities measurable in body fluids. Their presence or concentration must be linked to tumoral growth. The markers of the central nervous system tumors are detected in CSF. Alpha-feto-protein, carcinoembryonic antigen, human chorionic gonadotropin, adenohypophyseal peptide hormones, enzymes, etc., have found some application in the early diagnosis of leptomeningeal metastasis. Other applications involve the early detection and recurrency of primary brain tumors, as well as the evaluation of efficacy of their therapy. The tests based on the CSF content of desmosterol and polyamines have been studied extensively. Their rationale is discussed and specificity, sensitivity, efficiency and predictive value are considered. Experimental results concerning a new possible biochemical marker, based on CSF concentration of cyclic adenosine monophosphate, are reported.
Subject(s)
Brain Neoplasms/diagnosis , Cerebrospinal Fluid/analysis , Carcinoembryonic Antigen/cerebrospinal fluid , Desmosterol/cerebrospinal fluid , Diagnostic Errors , Humans , Nucleotides, Cyclic/cerebrospinal fluid , Polyamines/cerebrospinal fluid , alpha-Fetoproteins/cerebrospinal fluidSubject(s)
Astrocytoma/cerebrospinal fluid , Brain Neoplasms/cerebrospinal fluid , Glioblastoma/cerebrospinal fluid , Glioma/cerebrospinal fluid , Oligodendroglioma/cerebrospinal fluid , Sterols/cerebrospinal fluid , Animals , Astrocytoma/drug therapy , Brain Neoplasms/drug therapy , Cholesterol/cerebrospinal fluid , Chromatography, Gas , Culture Techniques , Desmosterol/cerebrospinal fluid , Glioblastoma/drug therapy , Glioma/drug therapy , Humans , Methotrexate/therapeutic use , Oligodendroglioma/drug therapy , Rats , Triparanol/therapeutic useSubject(s)
Brain Neoplasms/cerebrospinal fluid , Cholesterol/cerebrospinal fluid , Acute Disease , Astrocytoma/cerebrospinal fluid , Autoanalysis , Brain Neoplasms/diagnosis , Cholestanes/cerebrospinal fluid , Chromatography, Gas , Desmosterol/cerebrospinal fluid , Esters , Evaluation Studies as Topic , Follow-Up Studies , Glioblastoma/cerebrospinal fluid , Humans , Methods , TriparanolSubject(s)
Brain Neoplasms/cerebrospinal fluid , Enzymes/cerebrospinal fluid , Spinal Cord Neoplasms/cerebrospinal fluid , Adenylate Kinase/cerebrospinal fluid , Aspartate Aminotransferases/cerebrospinal fluid , Brain Neoplasms/diagnosis , Creatine Kinase/cerebrospinal fluid , Desmosterol/cerebrospinal fluid , Fructose-Bisphosphate Aldolase/cerebrospinal fluid , Glucose-6-Phosphate Isomerase/cerebrospinal fluid , Humans , Isocitrate Dehydrogenase/cerebrospinal fluid , L-Lactate Dehydrogenase/cerebrospinal fluid , Muramidase/cerebrospinal fluid , Polyamines/cerebrospinal fluid , Spinal Cord Neoplasms/diagnosisSubject(s)
Brain Neoplasms/cerebrospinal fluid , Spinal Cord Neoplasms/cerebrospinal fluid , Acid Phosphatase/cerebrospinal fluid , Brain Neoplasms/diagnosis , Carcinoembryonic Antigen/analysis , Chorionic Gonadotropin/cerebrospinal fluid , Creatine Kinase/cerebrospinal fluid , Desmosterol/cerebrospinal fluid , Glucuronidase/cerebrospinal fluid , Humans , L-Lactate Dehydrogenase/cerebrospinal fluid , Meningeal Neoplasms/diagnosis , Meningeal Neoplasms/secondary , Neoplasm Metastasis/diagnosis , Nucleotides, Cyclic/cerebrospinal fluid , Pituitary Hormones, Anterior/cerebrospinal fluid , Polyamines/cerebrospinal fluid , Somatostatin/cerebrospinal fluid , Spinal Cord Neoplasms/diagnosis , alpha-Fetoproteins/cerebrospinal fluidSubject(s)
Brain Neoplasms/cerebrospinal fluid , Desmosterol/cerebrospinal fluid , Glioma/cerebrospinal fluid , Astrocytoma/cerebrospinal fluid , Brain Neoplasms/drug therapy , Carmustine/therapeutic use , Cholesterol/cerebrospinal fluid , Chromatography, Gas , Desmosterol/analysis , Diagnosis, Differential , Ependymoma/cerebrospinal fluid , Humans , Lomustine/therapeutic use , Medulloblastoma/cerebrospinal fluid , Oligodendroglioma/cerebrospinal fluid , TriparanolABSTRACT
The cerebrospinal fluid levels of cholesterol, desmosterol, and the ratio 100 D:C taken from a study of 59 patients are reported. The patients, who had tumors of the nervous system, underwent neurosurgery, radiotherapy, and chemotherapy with 1,3-bis(2-chloroethyl)-1-nitrosourea or 1-(2-chlororethyl)-3-cyclohexyl-1-nitrosourea. The relationships among the levels of these three parameters and the clinical and neuroradiologic evolution are discussed.
Subject(s)
Antineoplastic Agents/pharmacology , Brain Neoplasms/cerebrospinal fluid , Cholesterol/cerebrospinal fluid , Desmosterol/cerebrospinal fluid , Adult , Brain Neoplasms/therapy , Carmustine/therapeutic use , Female , Humans , Lomustine/therapeutic use , Male , Middle AgedABSTRACT
The desmosterol test for the diagnosis of central nervous system (CNS) tumors is proposed in a simplified form. The procedure is based upon the analysis of sterol profile in cerebrospinal fluid (CSF) by selected ion monitoring (SIM) technique. Applied to 55 patients with tumoral and non tumoral CNS disease, the new test detects average levels of CSF desmosterol in tumor bearing patients that are tenfold higher than in the absence of CNS neoplasia. On an individual basis, a concentration of CSF desmosterol equal to or higher than the mean plus twice the standard deviation for the reference group of patients with no CNS tumor, is considered a positive result. Based on this criterion, a correct diagnosis was made in 73% of cases vs 77% of the former test, which required a 5-day treatment period with a desmosterol-reductase inhibitor in order to increase CSF desmosterol concentration. With this revised procedure CSF desmosterol can be detected in smaller volumes of CSF without any drug pretreatment, thus making the test more suitable for clinical application.
Subject(s)
Brain Neoplasms/diagnosis , Desmosterol/cerebrospinal fluid , Brain Neoplasms/cerebrospinal fluid , Chromatography, Gas , Evaluation Studies as Topic , Humans , Ions/analysis , Mass Spectrometry , MethodsABSTRACT
This study was an effort to obtain a marker indicative of the biologic activity of human gliomas. Sterol levels in the cerebrospinal fluid (CSF) were evaluated. Studies were conducted longitudinally during the course of tumor therapy. The evidence indicated that desmosterol levels in the CSF may reflect the growth potential of these neoplasms.