Protective properties of lysozyme on ß-amyloid pathology: implications for Alzheimer disease.

The hallmarks of Alzheimer disease are amyloid-ß plaques and neurofibrillary tangles accompanied by signs of neuroinflammation. Lysozyme is a major player in the innate immune system and has recently been shown to prevent the aggregation of amyloid-ß1-40 in vitro. In this study we found that patients with Alzheimer disease have increased lysozyme levels in the cerebrospinal fluid and lysozyme co-localized with amyloid-ß in plaques. In Drosophila neuronal co-expression of lysozyme and amyloid-ß1-42 reduced the formation of soluble and insoluble amyloid-ß species, prolonged survival and improved the activity of amyloid-ß1-42 transgenic flies. This suggests that lysozyme levels rise in Alzheimer disease as a compensatory response to amyloid-ß increases and aggregation. In support of this, in vitro aggregation assays revealed that lysozyme associates with amyloid-ß1-42 and alters its aggregation pathway to counteract the formation of toxic amyloid-ß species. Overall, these studies establish a protective role for lysozyme against amyloid-ß associated toxicities and identify increased lysozyme in patients with Alzheimer disease. Therefore, lysozyme has potential as a new biomarker as well as a therapeutic target for Alzheimer disease.

Cerebrospinal fluid lysozyme level for the diagnosis of tuberculous meningitis in children.

Lysozyme activity was assayed in the cerebrospinal fluid (CSF) of 32 tuberculous meningitis (TBM), 17 bacterial meningitis, 10 partially treated bacterial meningitis, 18 encephalitis and 18 control subjects. The mean CSF lysozyme activity was significantly raised (p < 0.001) in TBM patients compared with other study groups. A cut-off CSF lysozyme level of > or = 26 U/l had a sensitivity and specificity of 93.7 and 84.1 per cent, respectively for the diagnosis of TBM. Overall, it was found to be a better test than any other single test and thus can be used for rapid and early diagnosis of TBM in children.

Intrathecal synthesis of beta 2-microglobulin and lysozyme: differential markers of nervous system involvement in patients infected with human immunodeficiency virus type 1.

beta 2-Microglobulin and lysozyme were determined in paired serum and cerebrospinal fluid samples from 137 patients, using immunofluorometry and ELISA, respectively. Of these patients, 54 were infected by human immunodeficiency virus type 1 (HIV1) (including 20 AIDS dementia patients), 73 were HIV1-seronegative with neurological diseases (meningitis (n = 10), multiple sclerosis (n = 29), other neurological diseases (n = 34)) and 10 were controls. Intrathecal synthesis of beta 2-microglobulin occurred in each group. Conversely, lysozyme intrathecal synthesis was found only in meningitis (10/10) and in HIV1-infection (24/54). A pathological increase in beta 2-microglobulin intrathecal synthesis (> or = 2 mg/l) was observed in 45 patients (34 HIV1-infected patients and 11 HIV1-seronegative patients with neurological diseases). Serum concentration and intrathecal synthesis of beta 2-microglobulin were correlated only in the 20 AIDS dementia patients. The cerebrospinal fluid beta 2-microglobulin and lysozyme concentrations were correlated in the 54 HIV1-infected patients only. Blood CD4 + T-cell count was correlated negatively with beta 2-microglobulin intrathecal synthesis but not with lysozyme intrathecal synthesis. These data suggest that in the absence of any central nervous system opportunistic process the increase of beta 2-microglobulin intrathecal synthesis (> or = 2 mg/l) may be a reliable marker of central nervous system involvement in HIV1-infected patients. Intrathecal synthesis of lysozyme was related principally to HIV1-encephalitis and central nervous system opportunistic processes.

Age-related alterations of the blood-brain-barrier (bbb) permeability to protein molecules of different size.

Transfer processes of differently sized protein molecules across the blood-brain-barrier (bbb) were studied in "normal" , respectively, diseased elderly humans. Lumbar CSF/serum ratio of albumin contents increased significantly with age in a control group, but it was diminished in patients suffering from inflammatory or non-inflammatory diseases. Ratio of alpha 2-macroglobulin contents increased with age, especially in the diseased elderly. Concentration ratios of lysozyme, orosomucoid, lactoferrin, IgG, IgA and IgM decreased with age in a control group and especially decreased in a patient group. The data are discussed with respect to two different transfer processes which appeared to be altered in age and/or disease processes.

[The activities of 3 enzymes in serum and cerebrospinal fluid for diagnosis of tuberculous meningitis].

The adenosine deaminase (ADA), lysozyme (LZM) and lactate dehydrogenase (LDH) of serum and cerebrospinal fluid (CSF) were determined in 36 patients with tuberculous meningitis (TBM), 47 patients with non-tuberculous meningitis (N-T-BM) and 20 patients with non-central nervous system diseases(control group). The results showed that the assessment of serum and CSF ADA and LZM activity may be helpful to the differential diagnosis between TBM and N-TBM.

Analysis for cerebrospinal fluid proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Cerebrospinal fluid (CSF) proteins with molecular masses of < 150,000 Da were identified by immunoblotting after two kinds of nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). With PAGE 1 (17-27% gradient gel), CSF proteins were clearly separated into seven to nine bands with molecular masses of 3000-67,000 Da; seven bands were identified as beta 2-microglobulin, lysozyme, prealbumin, free kappa and lambda chain, apolipoprotein A-I, glycoproteins, and albumin by immunoblotting. With PAGE 2 (10-20% gradient gel), proteins were clearly separated into 11-16 bands with molecular masses of 15,000-150,000 Da; 11 were identified as prealbumin, free kappa and lambda chain, apolipoprotein A-I, glycoproteins, albumin, alpha 1-antitrypsin, transferrin (separated into two bands), immunoglobulin fragments, haptoglobin, and IgG. We analyzed CSF samples collected from 81 patients with cerebrospinal signs by these SDS-PAGE methods and observed prominent bands in some cases.

Cerebrospinal fluid levels of lysozyme, IgM and C-reactive protein in the identification of bacterial meningitis.

Lysozyme (LZM), immunoglobulin M (IgM) and C-reactive protein (CRP) levels were determined in cerebrospinal fluid (CSF) from patients classified on the basis of clinical and laboratory findings into three groups: bacterial meningitis (n = 33), lymphocytic meningitis (n = 21) and controls (n = 54). IgM and CRP levels were determined by enzyme-linked immunosorbent assay (ELISA) and LZM by the lysoplate method. Discriminant analysis demonstrated that 93.94% (31/33) and 96.97% (32/33) of patients with bacterial meningitis were correctly classified on the basis of CSF determinations of IgM and LZM, respectively. However, the measurement of CRP levels in CSF correctly classified 100% of these patients (33/33), thus representing a useful additional marker for the screening of bacterial meningitis. Moreover, no more than 4% (3/75) of patients were incorrectly classified as belonging to the bacterial group on the basis of the CRP test. Thus, CRP titres less than or equal to 80 identify cases belonging to one of the non-bacterial groups, whereas titres greater than or equal to 640 classify the bacterial group, with a very low chance of misclassification. The authors recommend that CSF IgM or LZM levels be also measured for patients with CSF CRP titres of 160 and 320, for a more accurate diagnosis. The probability of these cases being of bacterial aetiology, as calculated from the combined results of these measurements, is presented.

[The rapid differential diagnosis of bacterial and viral meningitis by using the lysozyme test]. / Differentsial'naia ékspress-diagnotika bakterial'nykh i virusnykh meningitov s pomoshch'iu lizotsimnogo testa.

The authors have modified the technique of the lysozyme test by adding polimixin M sulfate into the gel bacterial medium. Rapid diagnosis with the use of this test is based on different time of the appearance of the lysis areas: in bacterial meningitides the CSF lysozyme activity is detectable within 15-120 min, whereas in viral meningitides it manifests 40-50 min later or does not manifest at all. The results were found to depend on the time of the CSF collection: the earlier the CSF samples were obtained, the higher was the share of positive results.

Neurosarcoidosis without systemic sarcoidosis.

Neurosarcoidosis is a well-recognised complication of systemic sarcoidosis but diagnosis may be difficult if there is no clear evidence of an extracerebral manifestation of the disease. We present the case of a 42-year-old woman with clinical features characteristic of cerebral sarcoidosis including tetraparesis, diabetes insipidus, diencephalic hyperphagia, personality changes, and memory loss. Diagnosis was supported by cerebrospinal fluid (CSF) findings and magnetic resonance imaging (MRI): CSF showed mild lymphocytic pleocytosis, intrathecal production of IgG without oligoclonal bands, and a raised level of lysozyme. MRI revealed multiple contrast-enhanced granulomas at the base of the brain with partial involvement of diencephalic and mesencephalic structures and parts of the spinal cord. There was no evidence of systemic manifestation of sarcoidosis. Administration of corticosteroids led to improvement of the symptoms.

[Evaluation of the value of determining lysozyme levels in cerebrospinal fluid in myeloencephalitis]. / Ocena przydatnosci oznaczania stezenia lizozymu w plynie mózgowo-rdzeniowym w przebiegu zapalen opon mózgowo-rdzeniowych.

The study aimed at assessing the value lysozyme assay in CFS as indicator of the damage to blood-cerebrospinal fluid barrier and intensification of inflammatory process in the course of meningitis. The study involved 20 patients with suppurative and 66 with viral meningitis. Control group included 26 patients without nervous system disease. To estimate the degree of blood-cerebrospinal fluid barrier damage albumin and lysozyme indicators were calculated. It was proved, that CSF lysozyme levels are bigger in the suppurative meningitis than in viral meningitis. According to the author, CSF lysozyme levels the value of lysozyme indicator may inform on intensification of the inflammatory process and the degree of blood-cerebrospinal fluid barrier damage in suppurative meningitis, whereas in the viral meningitis they inform on degree of blood-cerebrospinal fluid barrier damage, only.

[Cerebrospinal fluid lysozyme in meningitis in children. Value in establishing the etiologic diagnosis]. / Le lysozyme du liquide céphalo-rachidien au cours des méningites de l'enfant. Intérêt dans l'orientation du diagnostic étiologique.

Cerebrospinal fluid lysozyme (CSF-LZM) concentrations were determined in 62 controls, 28 viral meningitis and 22 bacterial meningitis, as compared to CSF lactic acid routinely used. CSF-LZM measurement was performed by a rapid turbidimetric assay which required 50 microliters CSF only. The mean CSF-LZM concentration of the control group was 0.23 mg/l, the highest value being 0.65 mg/l. The mean LZM levels in viral meningitis were 1.10 mg/l, never exceeding 3 mg/l. The range of pretreatment LZM levels in bacterial meningitis was 7.2 to 65 mg/l and above 3 mg/l in all cases 48 h after treatment. On the 6th day after admission, 12 of 16 samples showed abnormal values. The CSF-LZM assay seems to be of more value than that of lactic acid. Thus, before treatment, LZM concentrations were 10 to 100 fold higher than that of the normal values, with persistent high levels on the 2nd and even on the 6th day of treatment (whereas lactic acid values were all normal on day 6).

New cerebrospinal fluid, neurophysiological and neuroradiological examinations in the diagnosis and follow-up of neurosarcoidosis.

For a complete evaluation of a patient with suspected neurosarcoidosis, combination of the newer CSF, neurophysiological, and neuroradiological studies is needed. CSF enzyme studies are useful in cerebral lesions and especially in cranial nerve lesions where CT and MRI usually fail to show abnormalities. Evoked potential examinations are a helpful noninvasive method for detection of both cerebral and cranial nerve lesions. Although CT and MRI are mainly abnormal in patients with cerebral symptoms they can disclose unexpected CNS involvement even in patients with mainly cranial nerve affection. However, even the newest diagnostic methods are nonspecific, and histologically verified systemic sarcoidosis still remains the mainstay of diagnosis.

Beta 2-microglobulin, lysozyme and lactoferrin in cerebrospinal fluid in patients with lymphoma or leukaemia: relationship to CNS involvement and the effect of prophylactic intrathecal treatment with methotrexate.

Central nervous system (CNS) involvement in patients with leukaemia or lymphoma presents a diagnostic problem. This study was conducted to test whether combined measurements of various cellular markers such as beta 2-microglobulin (beta 2m), lactoferrin (LF) and lysozyme (LYS) in the cerebrospinal fluid (CSF) might aid in the diagnosis of CNS involvement in such patients. Forty-two patients were studied. Sixteen were considered to have CNS involvement and 26 showed no signs of such involvement. In the group with symptoms or signs of CNS involvement, nine patients out of 12 had increased total protein in CSF, 14 of 14 increased beta 2m, 14 of 16 increased LYS and five of 15 increased LF. In patients without CNS involvement total protein was increased in four of 25, beta 2m in three of 21, LYS in four of 28 and LF in one of 28 patients. The differences were statistically significant (P less than 0.01, P less than 0.001, P less than 0.001 and P less than 0.05, respectively). Prophylactic intrathecal methotrexate treatment in patients with acute lymphoblastic leukaemia caused an increase in the CSF of beta 2m, LYS and LF but not of total protein, which may reflect a drug-induced inflammatory reaction in the CNS. We conclude that combined measurements of the three cell markers add to our understanding of the cellular reaction to malignant cells in the CNS in leukaemia and lymphoma and may be valuable supplements in the diagnosis of this CNS involvement.

Cerebrospinal fluid lysozyme and beta 2-microglobulin in neurosarcoidosis.

The levels of lysozyme (LZM) and beta 2-microglobulin (beta 2m) were measured in the cerebrospinal fluid (CSF) and serum of 32 patients with sarcoidosis, 20 of whom had neurosarcoidosis. LZM was analyzed by a new radioimmunoassay (RIA) modification. CSF LZM was elevated in 15 of 20 patients with neurosarcoidosis but in only 4 of 12 patients with extraneural sarcoidosis. CSF beta 2m values were elevated in 13 of 19 and in one of 11 patients, respectively. In neurosarcoidosis, both CSF LZM and beta 2m correlated to CSF leucocytes but not significantly to CSF albumin thus suggesting that LZM and beta 2m were secreted from cells within the central nervous system (CNS). In patients with sarcoidosis, elevations of CSF LZM and beta 2m revealed disease activity in the CNS. Both analyses were also useful in the follow-up of neurosarcoidosis.