Alterations of cholesterol precursor levels in Alzheimer's disease.

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.

Selected ion monitoring technique for the evaluation of sterols in cerebrospinal fluid: a new approach to desmosterol test for central nervous system tumors.

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.

Assessment of tumor markers in cerebrospinal fluid.

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.

[Markers of brain tumors]. / I marker dei tumori cerebrali.

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.

Biochemical markers of central nervous system tumors measured in cerebrospinal fluid and their potential use in diagnosis and patient management: a review.

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.

Cerebrospinal fluid sterols in the evaluation of patients with gliomas.

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.

Chemotherapy of human nervous system tumors: influence on cerebrospinal fluid sterols.

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.