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Biomedical subjects

K Blennow

Publications and source records attributed to K Blennow.

At least 145 records · Page 8Linked to original sources
PubMed1995

Detection of cerebrospinal fluid leakage by isoelectric focusing on polyacrylamide gels with silver staining using the PhastSystem.

Cerebrospinal fluid (CSF) leakage, which sometimes occurs after skull trauma, is a life-threatening condition. A prompt start with antibiotics and/or prompt surgical treatment of fistulas is essential to avoid severe complications. This requires a fast and reliable method for detecting CSF leakage. This paper describes a fast (< 2 h) method based on the identification of the tau protein (beta 2-transferrin) band(s). Tau protein is a brain-specific variant of transferrin that is characteristic of CSF. The method includes iso-electric focusing (IEF) on pre-cast polyacrylamide gels and silver staining using the PhastSystem, an automated instrument for electrophoresis and staining. In the present study, this technology was applied on 200 consecutive CSF samples, 32 of which were from healthy volunteers. Tau protein was detected in all CSF samples but 5 (2.5%), all of which were from patients with blood-brain barrier (BBB) damage. In these cases, the tau protein band was indistinct when direct silver staining was used. Therefore, immunofixation with an antitransferrin antibody was performed, and after that the tau protein band was easy to detect. The specificity of the method was high, since no brain-specific tau protein band was detected in serum, tears, saliva, or nasal secretion. As IEF of CSF using the PhastSystem is increasingly used as the routine method for detection of oligoclonal bands of IgG in neurological disorders, it could readily be used in the clinical (neuro) chemical laboratory also for the less frequent cases of suspected CSF leakage.

Adolescent↗
PubMed1995

Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease?

Cerebrospinal fluid (CSF) biochemical markers for Alzheimer disease (AD) would be of great value to improve the clinical diagnostic accuracy of the disorder. As abnormally phosphorylated forms of the microtubule-associated protein tau have been consistently found in the brains of AD patients, and since tau can be detected in CSF, two assays based on several well-defined monoclonal tau antibodies were used to study these proteins in CSF. One assay detects most normal and abnormal forms of tau (CSF-tau), while the other is highly specific for phosphorylated tau (CSF-PHFtau). A marked increase in CSF-PHFtau was found in AD (2230 +/- 930 pg/mL), as compared with controls (640 +/- 230 pg/mL; p < 0.0001), vascular dementia, VAD (1610 +/- 840 pg/mL; p < 0.05), frontal lobe dementia, FLD (1530 +/- 1000 pg/mL; p < 0.05), Parkinson disease, PD (720 +/- 590 pg/mL; p < 0.0001), and patients with major depression (230 +/- 130 pg/mL; p < 0.0001). Parallel results were obtained for CSF-tau. No less than 35/40 (88%) of AD patients had a CSF-PHFtau value higher than the cutoff level of 1140 pg/mL in controls. The present study demonstrates that elevated tau/PHFtau levels are consistently found in CSF of AD patients. However, a considerable overlap is still present with other forms of dementia, both VAD and FLD. CSF-tau and CSF-PHFtau may therefore be useful as a positive biochemical marker, to discriminate AD from normal aging, PD, and depressive pseudodementia. Further studies are needed to clarify the sensitivity and specificity of these assays, including follow-up studies with neuropathological examinations.

Aged↗
PubMed1994

Cerebrospinal fluid apolipoprotein E is reduced in Alzheimer's disease.

Apolipoprotein E (ApoE) has been implicated in the pathogenesis of Alzheimer's disease (AD). ApoE is synthesized within the brain and has been suggested to be involved in the re-utilization of membrane lipids during neuronal repair and remyelination after injury. Spherical ApoE-containing lipoprotein particles are found in the cerebrospinal fluid (CSF). To study further the pathogenetic role of ApoE in degenerative brain disorders, we analysed ApoE in CSF. A significant (p < 0.001) reduction of CSF ApoE (1.5 +/- 1.2 ng ml-1) was found in AD compared with controls (5.0 +/- 2.7 ng ml-1). A less pronounced reduction was also found in frontal lobe dementia (3.1 +/- 1.5 ng ml-1; p < 0.05). These findings support the hypothesis that ApoE is involved in the pathogenesis of degenerative brain disorders such as AD. An increased reutilization of ApoE-lipid complexes in the brain, as part of a generalized repair process, may explain the low CSF ApoE in AD. Alternatively, the reduction of CSF ApoE may be caused by absorption of ApoE to senile plaques and neurofibrillary tangles.

Aged↗
PubMed1994

Regulation of the hypothalamic-pituitary-adrenal axis in dementia disorders.

In 163 patients with dementia disorders, subdivided into Alzheimer's disease with early onset (AD; n = 40), senile dementia of the Alzheimer type (SDAT; n = 56), vascular dementia (VAD; n = 45) and dementia of unspecified type (NUD; n = 22) the dexamethasone suppression test (DST) was performed. The patients were rated according to the DSM-III-R criteria as having mild, moderate or severe dementia and were also assessed using the GBS scale which gives a profile of the dementia syndrome. In the total group of dementia there were significant correlations between severity of dementia and post-DST levels. The frequency of pathological DST also correlated significantly with the severity of dementia. In the subgroups of dementia a strong correlation between severity of dementia and high post-DST cortisol levels was found only in the VAD group. Between the subgroups of dementia disorders there were no significant differences in basal cortisol levels. The percentage of pathological DST was lowest in the AD group (40%). It was somewhat higher in the VAD group (49%), still higher in the SDAT group (54%) and highest in the NUD group (59%). When the relationship between post-DST cortisol levels and GBS scores was analyzed, significant correlations were found mainly in the VAD group. There intellectual impairment, anxiety, fear-panic and restlessness correlated significantly with post-DST cortisol levels. The results indicate hypothalamic overactivity in a substantial number of demented patients. In VAD and to a certain extent also in SDAT a disconnection between cortical areas, including the hippocampus, and the hypothalamus is assumed. Overactivity in the hypothalamic-pituitary-adrenal (HPA) axis is due to stress, and an insufficient feedback system leads to chronic stress adaptation failure.

Aged↗
PubMed1994

Neuron specific enolase in cerebrospinal fluid: a biochemical marker for neuronal degeneration in dementia disorders?

Alzheimer's disease (AD) is the most common disease causing dementia. Today the clinical diagnosis of AD is made by way of exclusion, and no biochemical markers are available to assist the clinical diagnosis. We examined the potential of neuron-specific enolase (NSE) in cerebrospinal fluid (CSF) as a diagnostic marker for AD. NSE was determined with a monoclonal antibody two-site immunoradiometric assay (IRMA) in serum (S) and cerebrospinal fluid (CSF) samples from 45 patients with "probable Alzheimer's disease (AD)", 19 patients with vascular dementia (VAD) and 33 age-matched healthy individuals. There was no significant correlation between S-NSE and CSF-NSE, or between CSF/S albumin ratio and CSF-NSE, findings suggesting that the major portion of CSF-NSE is intrathecally produced and that analysis of CSF-NSE alone (without accompanying analysis of serum) is sufficient. CSF-NSE was significantly higher in the AD group (4.7 +/- 2.7 ng/mL; p < 0.0001) and in VAD group (4.5 +/- 2.5 ng/mL; p < 0.001) as compared with the control group (2.2 +/- 1.0 ng/mL), while it did not differ significantly between the AD and the VAD group. These findings suggest that CSF-NSE have a potential as a non-disease specific marker for the neuronal degeneration in dementia disorders.

Aged↗
PubMed1994

Formulas for the quantitation of intrathecal IgG production. Their validity in the presence of blood-brain barrier damage and their utility in multiple sclerosis.

There are several formulas for the quantitative determination of intrathecal IgG production: Reiber and Felgenhauer's formula (IgG(loc)), the Extended IgG index, Tourtellotte's formula (TOURT), Schuller and Sagar's formula (SCHULL), the IgG index, the Log IgG index, and Blennow and co-workers' formula (IGGPROD). To evaluate the utility of these formulas in the presence of blood-brain barrier (BBB) damage, we present the results from a study of serum and cerebrospinal fluid (CSF) samples from 125 healthy individuals, 18-88 years of age; 1072 consecutive patients without oligoclonal IgG bands (OCBs) in the CSF, 683 without BBB damage (CSF/S: albumin ratio < 9.8) and 389 with BBB damage (CSF/S albumin ratio 9.8-30); and 106 patients with definite multiple sclerosis (MS). The relation between the CSF/S albumin ratio and the CSF/S IgG ratio was remarkably linear in both healthy individuals (r = 0.95; P < 0.0001) and patients without oligoclonal bands in the CSF (r = 0.95; P < 0.0001). Therefore, IgG(loc) and the Extended IgG index, two formulas based on a nonlinear relation between the CSF/S albumin ratio and the CSF/S IgG ratio, yielded biased results (lower values) in the presence of BBB damage. TOURT and SCHULL also yielded biased (higher) values in the presence of BBB damage, probably because of incorrect constants in these formulas. There were no significant correlations between the CSF/S albumin ratio (i.e. the BBB function) and the IgG index or the Log IgG index, two dimensionless quotients for the detection of intrathecal IgG production, or between the CSF/S albumin ratio and IGGPROD, an empirical formula for the determination of intrathecal IgG production in mg/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Immunomodulating and anti-inflammatory properties of the sympatholytic compound 6-hydroxydopamine.

The objective of this study was to analyse the anti-inflammatory and immunosuppressive properties of 6-hydroxydopamine (6-OHDA), a well known sympatholytic compound. Collagen type II arthritis, a T cell-dependent autoimmune disease, was significantly suppressed by a short-term administration of 6-OHDA at the time of the disease onset. Similar outcome was observed when in vivo models of T cell-dependent and independent inflammatory reactions were applied. In contrast, long-term pretreatment with 6-OHDA and hence efficient sympatholysis did neither affect the course of arthritis nor the outcome of T cell-dependent and independent inflammatory reactions. These findings, together with evidence of dose-dependent in vitro inhibitory effects of 6-OHDA on lymphocyte proliferation and differentiation, indicate that the anti-inflammatory features of this compound are mediated through a direct action on effector cells rather than by sympatholysis.

Animals↗
PubMed1994

Ubiquitin in cerebrospinal fluid in Alzheimer's disease and vascular dementia.

Ubiquitin (Ub) was determined by a competitive enzyme-linked immunosorbent assay (ELISA) in serum (S) and cerebrospinal fluid (CSF) samples from 29 patients with 'probable Alzheimer's disease' (AD), 14 patients with vascular dementia (VAD), and 13 healthy individuals. The mean concentration of Ub in CSF (110 +/- 20 ng/mL) was about 20% of that in serum (940 +/- 120 ng/mL) in healthy controls. There was no significant correlation between S-Ub and CSF-Ub, or between the CSF/S.Ub ratio and the CSF/S albumin ratio. These findings suggest that a major portion of CSF-Ub is intrathecally produced. CSF-Ub was increased while S-Ub was decreased in both AD and VAD patients as compared with controls. As a consequence, the CSF/S Ub ratio showed good discrimination between patients and controls: 22/29 (76%) of the AD patients and 9/14 (64%) of the VAD patients had a CSF/S Ub ratio that was higher than the highest control value. No significant differences in any of the parameters were found between AD and VAD. Ub is involved in an ATP-dependent proteolytic pathway and also acts as a heatshock protein. The increase in CSF-Ub in AD and VAD may therefore be interpreted as a cytoprotective response to abnormal or damaged proteins, and CSF-Ub may have a potential as a non-disease-specific marker for cerebral degeneration.

Aged↗
PubMed1994

Altered blood-brain-barrier function in Alzheimer's disease?

Alzheimer's disease (AD) and vascular dementia (VD) are the two most common causes of dementia. As yet, no definitive biological antemortem marker has been established for differential diagnosis of AD or VD. In this study, proteins of cerebrospinal fluid (CSF) from AD, VD and control patients were analyzed by two-dimensional (2-D) electrophoresis with immobilized pH gradients in the first dimension. No specific changes for AD or VD could be detected in the 2-D CSF patterns. However, a spot of haptoglobin alpha-1 chains (13.5 kDa; approximate pI 4.6) was found to be present in the majority of 2-D CSF maps from the dementia cases, suggesting a high-molecular-weight transudate type of alteration in the blood-brain barrier with considerable frequency in AD.

Aged↗
PubMed1994

Hypothalamic dysfunction in dementia.

In 40 patients with Alzheimer's disease (AD) 56 patients with senile dementia of Alzheimer type (SDAT) and 45 patients with vascular dementia (VAD) degree of dementia was rated into mild, moderate and severe according to DSM-III-R and on the GBS scale. Basal cortisol levels were determined and a dexamethasone test (DST) performed. Basal cortisol levels were high in all the dementia groups. Forty percent of AD patients, 54% of SDAT patients and 49% of VAD patients were non suppressors. Significant correlations between post DST cortisol levels and rated variables were seen mainly in the VAD group. The pathological DST could hardly be explained by presence of depression. In dementia, especially those with white matter disturbances, disconnections between cortical areas (hippocampus) and hypothalamus can be assumed explaining a reduced inhibitory tone on hypothalamus. When characterizing VAD patients with pathological DST these patients were significantly more intellectually impaired, showed higher degree of anxiety, restlessness and fear-panic than VAD patients with normal DST. Some behaviourial disturbances in dementia disorders may be a consequence of HPA over activity rather than a consequence of the dementia process itself.

Aged↗
PubMed1993

Concentration gradients for monoamine metabolites in lumbar cerebrospinal fluid.

Concentration gradients in lumbar cerebrospinal fluid (CSF) for the monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) were studied in 9 healthy controls and 47 neuropsychiatric patients without diseases causing disturbed CSF circulation. In a serial sampling of the first 24 ml of CSF, steep concentration gradients between the first (0-4th ml) and last (21st-24th ml) portions of CSF were found for HVA (99 +/- 59% increase; p < 0.001) and 5-HIAA (88 +/- 54% increase; p < 0.001), while the concentration gradient was slight for HMPG (11 +/- 7% increase; p < 0.001). The existence of marked concentration gradients for the monoamine metabolites HVA and 5-HIAA gives further evidence for an active transport system for these metabolites and indicates that the lumbar CSF-HVA and 5-HIAA levels reflect the dopamine and serotonin metabolism in the brain. Moreover, the existence of pronounced concentration gradients for HVA and 5-HIAA stresses the importance of making analyses on a standardized volume of CSF.

Adolescent↗
PubMed1993

Cerebrospinal fluid monoamine metabolites in 114 healthy individuals 18-88 years of age.

Concentrations of the monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) were determined in lumbar cerebrospinal fluid (CSF) of 114 healthy individuals, 18-88 years of age, without histories, symptoms or signs of central nervous system dysfunction. The mean values (+/- SD) were 253 +/- 109 nmol/l for HVA, 125 +/- 54 nmol/l for 5-HIAA, 47 +/- 10 nmol/l for HMPG, and 2.10 +/- 0.52 for the HVA/5-HIAA ratio. Analyses of confounding factors revealed that all metabolites correlated negatively with body height, the values being lower in taller than in shorter individuals. This is probably attributable to a larger surface area for monoamine metabolite transport from the subarachnoid space in taller than in shorter individuals. These correlations make statistical adjustment for body height important in analyses of monoamine metabolite levels. Without considering body height, all monoamine metabolites showed a positive correlation with age, and higher levels of HVA and 5-HIAA were found in women than men. After statistical adjustment for the influence of body height, no differences in CSF monoamine metabolites levels were found between the sexes, and only 5-HIAA showed a positive correlation with age. There were no significant seasonal variations for any of the monoamine metabolites.

Adolescent↗
PubMed1993

Low blood pressure and blood glucose levels in Alzheimer's disease. Evidence for a hypometabolic disorder?

OBJECTIVE: To test possible differences between patients with Alzheimer's disease (AD) and patients with other forms of dementia and the healthy population concerning body composition, blood pressure, metabolic data and leukoaraiosis (LA). DESIGN: Retrospective study on data collected according to a predefined protocol. SETTING: A geriatric, neuropsychiatric diagnostic unit. SUBJECTS: Seventy-one consecutive patients with dementia. MAIN OUTCOME MEASURES: Body mass index, blood pressure, metabolism and LA in AD compared to other dementia forms. RESULTS: Mean blood pressure and fasting blood glucose levels were lower in patients with AD, 94 +/- 12 mmHg and 4.3 +/- 0.5 mmol l-1, compared to patients with unspecified dementia (NUD), 100 +/- 10 mmHg and 5.5 +/- 2.5 mmol l-1 (P < 0.05) and vascular dementia (VAD), 114 +/- 12 mmHg and 5.6 +/- 1.6 mmol l-1 (P < 0.001) and the age-matched healthy population. Body mass index, serum cholesterol and cortisol were similar in all groups of dementia patients whereas triglycerides were highest in the VAD group. No cases of diabetes or treatment for hypertension were found in the AD group while the prevalence was 21% and 36% for diabetes in the NUD and VAD groups and 8% in the population from the same region. There were 16% with antihypertensive treatment in dementia NUD, 50% in VAD, and 30% in the general population. Treated or newly detected hypothyreosis was present in 11% of the AD patients, none in the other dementia groups and 2% in the general population. Smoking was least common in AD. Degree of LA correlated with blood pressure and blood glucose levels. CONCLUSIONS: AD was clearly different to other dementia patients. They had lower blood pressure, blood glucose and higher prevalence of hypothyreosis than the healthy, age-matched population. These findings may indicate that AD could be a hypometabolic disorder.

Aged↗
PubMed1993

Low frequency of post-lumbar puncture headache in demented patients.

The frequency of post-lumbar puncture headache (PLPH) was registered prospectively in 395 consecutive demented patients at a dementia diagnostic unit. The incidence of PLPH was low, occurring in only 8 patients (2.0%), the severity was mild, and the duration was less than 2 days in all cases but one. The reasons for this low frequency of PLPH in patients with dementia disorders may include disease- and/or age-related low pain sensitivity, rigid dural fibres and arteriosclerotic vessels, and large CSF space due to cerebral atrophy. Analysis of CSF is essential to identify secondary causes of dementia, preferentially chronic infections. The low frequency and severity of PLPH found in the present study shows that, with low risk of complications, lumbar puncture can be included in the routine clinical examination of demented patients.

Adult↗
PubMed1993

Protein analyses in cerebrospinal fluid. I. Influence of concentration gradients for proteins on cerebrospinal fluid/serum albumin ratio.

Concentration gradients in lumbar cerebrospinal fluid (CSF) for albumin and IgG were studied in 8 healthy individuals and 44 neuropsychiatric patients by serial sampling of 6 successive portions of CSF, each containing 4 ml, in all 24 ml. Significant and identical decreases between the first (0-4th ml) and the last (21st-24th ml) portions were found for CSF-albumin (21% decrease, p < 0.0001) and CSF-IgG (21% decrease, p < 0.0001). Therefore, the CSF/serum albumin ratio also showed a significant gradient with a 21% decrease (p < 0.0001), while no gradients were found to the IgG index. These results imply that analyses of proteins in the CSF should be performed on a standardized volume of CSF, preferably the first 12 ml, to allow comparisons of scientific results between various patient groups and controls and between different laboratories and to increase the validity of protein analyses in clinical practice.

Adolescent↗
PubMed1993

Protein analysis in cerebrospinal fluid. II. Reference values derived from healthy individuals 18-88 years of age.

Analyses of the cerebrospinal fluid (CSF) to determine the blood-CSF barrier function and to detect intrathecal IgG production are used in the diagnosis of neurological and psychiatric diseases. Therefore, accurate reference values for these parameters are of utmost importance. However, current reference values are based on 'reference groups' consisting of patients with psychiatric and/or neurological symptoms but without positive clinical findings and on groups of young students. The present study presents reference values for CSF proteins in a large sample (n = 105) of healthy individuals, with a large age-span (18-88 years of age). The parameter for the determination of the blood CSF barrier function, the CSF/serum (CSF/S) albumin ratio, was found to show an increasing variability in individuals over 45 years of age, suggesting a less stable blood-CSF barrier function than in younger individuals. The upper reference limit for the CSF/S albumin ratio was 6.8 for individuals under 45 years of age and 10.2 for individuals over 45 years of age. The IgG index, a dimensionless quotient for the determination of intrathecal IgG production, showed only a minor correlation with age and had an upper reference limit of 0.63.

Adolescent↗
PubMed1993

Protein analysis in cerebrospinal fluid. III. Relation to blood-cerebrospinal fluid barrier function for formulas for quantitative determination of intrathecal IgG production.

To examine the possible influence of the blood-CSF barrier function on mathematical formulas for estimating intrathecal IgG production (IgG index, Tourtellotte's formula [TOURT], Schuller and Sagar's formula [Schull], and Reiber and Felgenhauer's formula [IgG(loc)]), we analysed serum and CSF samples from 105 healthy individuals, aged 18-88 years, and 816 consecutive patients without oligoclonal IgG bands (OCBs) in the CSF, aged 18-91 years. In healthy individuals there was no significant correlation between the CSF/serum (S) albumin ratio (i.e. blood-CSF barrier function) and the IgG index, a dimensionless quotient for determining intrathecal IgG production, and only a small correlation (r = -0.08, p < 0.05) in patients without OCBs. However, significant dependence on the blood-CSF barrier function was found, in both healthy individuals and patients without OCBs, for the formulas determining intrathecal IgG production in milligrams (per litre CSF or per day), i.e. for TOURT, SCHULL and IgG(loc). Therefore, we propose a new formula for the quantitative determination of intrathecal IgG production in mg/l, the IGGPROD, which is calculated as: CSF-IgG -[(0.51 x CSF-Alb x S-IgG)/S-Alb]. IGGPROD is an empirical formula, based on findings in 105 healthy individuals 18-88 years of age, and does not depend on the blood CSF barrier function.

Adolescent↗