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K Blennow

Publications and source records attributed to K Blennow.

At least 127 records · Page 7Linked to original sources
PubMed1997

A new procedure for detecting brain-specific proteins in cerebrospinal fluid.

We have developed a new procedure, including three affinity chromatography steps, micro-reversed phase high pressure liquid chromatography (mR-HPLC) and Western blotting/mass spectrometric analysis to study central nervous system (CNS) specific proteins in human cerebro spinal fluid (CSF) in order to find biochemical markers for neuronal and synaptic function and pathology in degenerative brain disorders. After the three affinity chromatography steps, intended to remove interfering serum proteins from CSF, mR-HPLC revealed four major peaks, which by both Western blotting and mass spectrometric analyses were found to correspond to beta 2-microglobulin, cystatin C, transthyretin (TTR) and asialotransferrin. When comparing these peaks in CSF from Alzheimer's disease (AD) patients and age-matched healthy controls, a reduction of the brain-specific TTR was found. Therefore we quantified TTR in CSF and serum samples from 8 patients with early onset AD (EAD), 18 patients with late onset AD (LAD), 8 patients with vascular dementia (VAD) and 18 healthy individuals using a nephelometric method. CSF-TTR was divided into barrier-dependent and barrier-independent TTR. The barrier-independent i.e. brain-specific TTR was significantly reduced in the EAD group compared to the controls. Transthyretin has been found to be present in the senile plaques in AD, and to specifically bind to beta/A4 protein, the major component of the amyloid deposits in AD. Therefore, the reduction of the transthyretin-isoform in CSF in AD may reflect an absorption of transthyretin to the amyloid deposits in the senile plaques.

Aged↗
PubMed1996

Synaptic pathology in Alzheimer's disease: relation to severity of dementia, but not to senile plaques, neurofibrillary tangles, or the ApoE4 allele.

Alzheimer's disease (AD) is characterised by an increased number of senile plaques (SP) and neurofibrillary tangles (NFT) as compared with that found in non-demented individuals of the same age, and a marked degeneration and loss of synapses. One of the main risk-factors for the disorder is inheritance of the apolipoprotein E4 (ApoE4) allele. To further study the relation between these pathogenetic substrates for AD, we quantified the synaptic vesicle membrane protein rab3a in brain tissue from 19 patients with AD and 9 age-matched control subjects. Rab3a levels were reduced in AD, both in the hippocampus (60% of control level, p < 0.0001), and in the frontal cortex (68% of control level, p < 0.01), but not in the cerebellum (92% of control level). Within the AD group, lower rab3a levels were found both with increasing duration and severity of dementia. These findings further support that synaptic pathology is closely correlated to the clinical dementia in AD. In contrast, no significant correlations were found between SP counts and duration or severity of dementia, while higher NFT counts in the frontal cortex were found with increasing severity of dementia (r = 0.54, p < 0.05). There were no significant correlations between the rab3a level and SP or NFT counts, and by immunohistochemistry, reduced rab3a immunostaining was found throughout the neuropil in AD brain, without relation to SP or NFT. These findings suggest that the synaptic pathology in AD is not closely related to the presence of SP and NFT. No significant differences in rab3a levels were found in any brain region between AD patients possessing different numbers of the ApoE4 allele, suggesting that, although ApoE4 is A risk factor for earlier development of AD, the degree of synaptic pathology does not differ between patients with or without the ApoE4 allele.

Aged↗
PubMed1996

Brain monoaminergic and neuropeptidergic variations in human aging.

The effect of age on the monoamines 5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine (DA), their metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 3,4-dihydroxphenylacetic acid (DOPAC), and the 5-HT precursor 5-hydroxy-L-tryptophan (5-HTP), together with the peptides neuropeptide Y (NPY), somatostatin (SOM), and corticotropin-releasing factor (CRF), was studied in frontal cortex, gyrus cinguli and hypothalamus from 23 healthy control subjects, aged 16-75 years. After correcting for postmortem interval, significant decreases in gyrus cinguli NA, NPY and CRF, and hypothalamic DA, HVA, and 5-HIAA concentrations were obtained with advancing age. The involvement of the monoaminergic system in several functional abnormalities appearing in senescence is suggested. Furthermore, evidence is given of the participation of the peptidergic systems in the aging process.

Adolescent↗
PubMed1996

Synaptotagmin, a synaptic vesicle protein, is present in human cerebrospinal fluid: a new biochemical marker for synaptic pathology in Alzheimer disease?

Using a novel approach, including affinity chromatography, reversed-phase chromatography, and chemiluminescence immunoblotting, we have for the first time been able to demonstrate one of the small synaptic vesicle proteins, synaptotagmin I, in cerebrospinal fluid (CSF). Two other small synaptic vesicle proteins, rab3a and synaptophysin, were not detectable. The approximate molecular weight of CSF-synaptotagmin was 65 kDa, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Further characterization of CSF synaptotagmin by high-performance capillary electrophoresis (HPCE) showed a single peak. These findings support that the whole synaptotagmin molecule is present in CSF, without significant proteolytic degradation. After high-speed centrifugation of CSF, synaptotagmin was exclusively found in the supernatant, suggesting that synaptotagmin is present in CSF as a free protein, and not as a constituent of synaptic vesicles. In a preliminary study, we found a marked reduction of CSF synaptotagmin in patients with early onset Alzheimer disease (EAD) as compared with age-matched healthy individuals. To elucidate the biological relevance of this finding, we also quantified synaptotagmin in brain tissue. A marked reduction in synaptotagmin was found both in the hippocampus and frontal cortex of EAD, suggesting that a decrease in synaptotagmin in the brain is followed by a concomitant decrease in the CSF. Analysis of CSF synaptotagmin might provide a tool to study synaptic function and pathology in the human brain.

Aged↗
PubMed1996

Differences in the neuropeptide Y-like immunoreactivity of the plasma and platelets of human volunteers and depressed patients.

In this study, patients with recurrent major depression were found to have significantly lower neuropeptide Y-like immunoreactivity (NPY-LI) in platelet-poor plasma (p < 0.01) and significantly higher NPY-LI in platelets (p < 0.001) compared to controls. Also, qualitative differences in the NPY-LI in platelet-poor plasma (PPP) and platelets were detected when the samples were analyzed by HPLC followed by RIA of the collected fractions.

Adult↗
PubMed1996

Impairment of the blood-CSF barrier in suicide attempters.

In a patient group of 90 suicide attempters, 18% showed an impaired blood-CSF barrier; of these 16 patients, all but one were younger than 45 years. When compared with 105 healthy controls, a significant difference in impairment of the blood-CSF barrier, between patients and controls, was seen only in those younger than 45 years (z = -2.66; P < 0.01). Paracetamol intoxication was more common among those with an impaired blood-CSF barrier than among those without an impairment (Fisher's exact test, P = 0.00029). Paracetamol intoxication was the most common method of suicide attempt in patients with adjustment disorders. There was no significant association between alcohol and/or drug abuse and an impaired blood-CSF barrier (Fisher's exact test, P = 0.91977). There were no differences in IgG index between patients and controls. The hypothesis that a blood-CSF barrier leakage may be a confounding factor when assessing the levels of monoamine metabolites in the CSF did not receive any support.

Adult↗
PubMed1996

Decreased lumbar cerebrospinal fluid levels of monoamine metabolites in vascular dementia.

The levels of the monoamine metabolites 5-hydroxy-indoleacetic acid (5-HIAA), homovanillic acid (HVA), and 4-hydroxy-3-methoxy-phenylglycol (HMPG) were determined in lumbar cerebrospinal fluid (CSF) of 56 patients with vascular dementia (VAD) and 57 healthy controls. Despite CSF sampling under standardized conditions, the variability in values was wide among both patients and controls. This suggests that yet unknown factors affect the lumbar CSF concentrations of monoamine metabolites. The VAD group showed significantly lower mean concentrations of 5-HIAA (p < .001) and HVA (p < .001) than the control group. These low concentrations appear to be no disease-specific phenomenon, but may be attributable to subcortical white-matter changes or a decreased production of monoamines, which are dependent on oxygen for their synthesis.

Aged↗
PubMed1996

The neurochemistry of Alzheimer's disease.

The last 15-20 years have seen a wealth of studies to characterize the neurochemical abnormalities of Alzheimer's disease, in particular those involving the beta-amyloid and tau proteins, as well as more recently, apolipoprotein E4. This article provides a summary of the evidence for the involvement of these proteins in Alzheimer's disease pathogenesis based on postmortem brain and CSF studies.

Aged↗
PubMed1996

Clinical subgroups of the Alzheimer syndrome.

During the last decade, senile dementia and the presenile disease that was named after Alois Alzheimer have been considered a single entity called Alzheimer's disease (AD). This same decade has witnessed the development of many diagnostic tools, such as CT, MRI, and SPECT imaging, that have made possible the systematic analysis of symptoms of brain disorders. With the aid of these sophisticated techniques, it is possible to divide the disorder into clinically relevant subgroups, one of which corresponds to the disease first described by Alzheimer. The disease exists in sporadic and familial forms, and in subgroups of these two basic types. Because the heterogeneity of AD is incontestable, it is time to reconsider the current use of the term "Alzheimer's disease." Because it labels different subgroups whose characteristics are often markedly different, the term "Alzheimer syndrome" appears to be more appropriate.

Alzheimer Disease↗
PubMed1996

The apolipoprotein E allele epsilon 4 does not correlate with the number of senile plaques or neurofibrillary tangles in patients with Alzheimer's disease.

BACKGROUND AND OBJECTIVES: Apolipoprotein E (apoE) has been implicated in regenerative processes in the brain after trauma, as well as in the pathogenesis of Alzheimer's disease. Inheritance of a specific apo epsilon allele (apo epsilon 4) determines in part the risk and the mean age at onset of Alzheimer's disease. ApoE has been found to bind isoform specifically to beta-amyloid protein, the major component of senile plaques, and to the microtubule associated protein tau, which forms paired helical filaments and neurofibrillary tangles. The aim was to further examine the relation between apo epsilon alleles, especially apo epsilon 4, and the development of neuropathological changes associated with Alzheimer's disease. METHODS: Brains of patients with Alzheimer's disease (n = 44) and vascular dementia (n = 11) and of age matched controls (n = 29) were studied. Senile plaques and neurofibrillary tangles in the hippocampus and frontal cortex were quantified. RESULTS: No correlation was found between the number of apo epsilon 4 alleles and the number of senile plaques and neurofibrillary tangles in the hippocampus or the frontal cortex of patients with Alzheimer's disease, or vascular dementia, or control groups. No significant differences in duration or severity of dementia were found between patients with or. without the apo epsilon 4 allele. No increased frequency of apo epsilon 4 was found in vascular dementia. CONCLUSION AND COMMENT: Although the apo epsilon genotype clearly affects whether Alzheimer's disease will develop or not, the present study suggests that it has no influence on pathology or clinical intellectual status, once the dementia has manifested itself. No increased apo epsilon 4 allele frequency was found in neuropathologically diagnosed patients with vascular dementia in whom concomitant Alzheimer's disease can be excluded.

Aged↗
PubMed1996

Immunoglobulin M in cerebrospinal fluid: reference values derived from 111 healthy individuals 18-88 years of age.

The importance of immunoglobulin M (IgM) determination in cerebrospinal fluid (CSF) has increased parallel to the need for early diagnosis of infectious and inflammatory disorders of the central nervous system. Current reference values are based on analysis of CSF from 'reference groups' consisting of patients with psychiatric and/or neurological symptoms but without positive clinical findings. Therefore, accurate reference values for CSF IgM are of utmost importance. The present study presents reference values for IgM in CSF in a large sample (n = 111) of healthy individuals with an age span of 18-88 years. The upper reference limit, calculated as the 0.95 fractile, was 0.36 mg/l for CSF IgM, 0.40 for CSF/serum IgM ratio, and 0.045 for the IgM index. These parameters showed no significant difference between sexes nor any significant correlations with age. The correlations between CSF/serum albumin ratio and CSF/S IgM ratio were linear and statistically highly significant, suggesting that the IgM index values do not depend on the blood-CSF barrier function within the normal range of the CSF/serum albumin ratio.

Adolescent↗
PubMed1996

Stepwise comparative status analysis (STEP): a tool for identification of regional brain syndromes in dementia.

A method for clinical examination of patients with dementia, stepwise comparative status analysis (STEP), is presented. It combines psychiatric and neurologic status examination methods to identify certain common dementia symptoms by which the patient's regional brain symptom profile can be determined. Fifty status variables (items) are estimated with respect to occurrence and severity. The analysis is performed in three steps. The scores on the 'primary' variables reflect observations of single dementia symptoms. These scores form the basis for the assessment of the 'compound' variables, which in turn form the basis for evaluation of the 'complex' variables, one of which describes the patient's regional (predominant) brain syndrome (subcortical, frontosubcortical, frontal, frontoparietal, parietal, or global). In 96 mildly and moderately demented inpatients, the global (42%) and frontosubcortical (31%) were the most common. Ninety-one percent of the patients with vascular dementia had a predominant frontal and/or subcortical symptomatology.

Aged↗
PubMed1996

The concentrations of monoamine metabolites and neuropeptides in the cerebrospinal fluid of obese women with different body fat distribution.

DESIGN AND SUBJECTS: Several studies suggest neuroendocrine abnormalities in, particularly, abdominal, central obesity in humans, a condition with high morbidity and mortality. Therefore the concentrations of neuropeptides and catecholamines in cerebrospinal fluid (CSF) were analysed in 48 obese women, subdivided into groups with central, abdominal and gluteo-femoral distribution of body fat, utilising the waist-to-hip circumference ratio (WHR) for division. RESULTS: In comparisons with non-obese control women concentration of 5-hydroxyindol acetic acid (5-HIAA), methoxyhydroxyphenylglycol (MHPG), corticotropin releasing hormone (CRH), beta-endorphins (END) and neuropeptide Y (NPY) were lower, while homovanillic acid (HVA) was not different in obese women, HIAA, HVA and END correlated negatively with the WHR only in abdominally obese women, suggesting a threshold effect. HIAA vs HVA as well as CRF vs END correlated strongly in the total and both subgroups. An interrelationship between all these four substances was found in abdominal but not in gluteo-femoral obesity, suggesting a tighter functional coupling in the former group. Several correlations were found between CSF substance levels and appetite registrations, including END vs voracious eating, and for carbohydrate craving vs HIAA and vs HVA (negatively). This was also found only in abdominally obese women. CONCLUSION: Although the concentrations of monoamine metabolites and neuropeptides in the CSF sampled at the level of the lumber spine might not be representative for those at regulatory centers in the brain, the findings suggest that low 5-HIAA is characteristic of human obesity, and coupled to CRH as well as eating abnormalities, particularly in abdominal obesity. Since CRH is regulating the balance between the autonomic nervous systems, insulin secretion and thermogenesis in animals, corresponding anomalies in abdominal obesity in humans may have a central origin.

Adipose Tissue↗
PubMed1995

Cerebrospinal fluid neuropeptides in Alzheimer's disease and vascular dementia.

Cerebrospinal fluid (CSF) levels of several neuropeptides have been suggested as candidate markers in neurodegenerative disorders. We have examined the levels of corticotropin-releasing hormone (CRH), beta-endorphine (BEND), delta sleep-inducing peptide (DSIP), somatostatin (SRIF), and neuropeptide Y (NPY) in CSF samples obtained under highly standardized conditions from healthy aged controls and from patients suffering from Alzheimer's disease (AD) or vascular dementia (VAD). The influence of some potentially confounding factors was evaluated. CRH and BEND were markedly decreased in both AD and VAD patients, and BEND levels correlated negatively with degree of dementia within the patient population. SRIF was decreased in both AD and VAD patients. DSIP was slightly increased in AD, but not in VAD. NPY did not differ between groups. For none of the peptides did CSF concentrations correlate significantly with duration of illness, nor, with the exception of BEND, with its degree. Present data do not support the hypothesis that specific neuropeptide changes occur in different neurodegenerative disorders, but are in agreement with previous reports suggesting that neuropeptide systems are differentially affected by neurodegeneration.

Aged↗
PubMed1995

Cerebrospinal fluid 'neuronal thread protein' comes from serum by passage over the blood-brain barrier.

Cerebrospinal fluid (CSF) biochemical markers for Alzheimer's disease (AD) would be of great value, both to improve clinical diagnostic accuracy and to increase our knowledge of the pathogenesis of the disorder. An increase in the CSF-level of 'neuronal thread protein' (pancreatic thread protein (PTP) immunoreactive material in the brain) has been suggested to be just such a biochemical marker. We have studied CSF 'neuronal thread protein'-like immunoreactivity (NTPLI) using a microparticle enzyme immunoassay. CSF-NTPLI did not differ significantly between AD type I (pure AD) and controls, but was significantly higher in AD type II (senile dementia) and vascular dementia (VAD) as compared with controls. Signs of blood-brain barrier (BBB) damage (elevated CSF/S albumin ratio) were found in both AD type II and in VAD, but not in AD type I. In a multiple ANOVA, with age and CSF/S albumin ratio as covariates, no significant difference in CSF-NTPLI between diagnostic groups was noted though both CSF/S albumin ratio and age (P < 0.0001 and P < 0.001 respectively) were found to influence the CSF-NTPLI level. Since BBB function was found to influence the CSF-NTPLI level, we examined whether NTPLI was present in serum. Indeed, serum NTPLI was about 40 times higher than CSF-NTPLI in neurological patients. Moreover, there was a statistically significant correlation between S-NTPLI and CSF-NTPLI. Taken together, present findings suggest that most of NTPLI in CSF comes from the serum, by passage over the BBB.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

A population-based study of tau protein and ubiquitin in cerebrospinal fluid in 85-year-olds: relation to severity of dementia and cerebral atrophy, but not to the apolipoprotein E4 allele.

Alzheimer's disease (AD) is the most common form of dementia, and is characterized by a degeneration of neurones and their synapses, and a higher number of senile plaques (SP) and neurofibrillary tangles (NFT) compared with that found in non-demented individuals of the same age. NFT are composed of a hyperphosphorylated and ubiquitinated form of tau protein. Previous studies have found that in the cerebrospinal fluid (CSF) both tau and ubiquitin are increased in AD. We examined CSF-tau and CSF-ubiquitin in a population based sample of 85-year-olds, 26 demented (11 with probable Alzheimer's disease (AD), 13 with probable vascular dementia (VAD) and 2 with mixed (AD/VAD) type of dementia) and 35 non-demented individuals. CSF-tau was significantly higher both in the probable AD group (254 +/- 113 pg/mL; P < 0.01), and in the probable VAD group (247 +/- 75 pg/mL; P < 0.005), than in the non-demented group (171 +/- 78 pg/mL), but did not significantly differ between the probable AD and probable VAD groups. In contrast, CSF-ubiquitin did not significantly differ between the probable AD (100 +/- 24 ng/mL), probable VAD (102 +/- 16 ng/mL), and non-demented (97 +/- 27 ng/mL) groups. CSF-tau increased with increasing severity of dementia (P < 0.001), though no such relation was found for CSF-ubiquitin. Neither CSF-tau nor CSF-ubiquitin differed between patients with or without the apolipoprotein E E4 isoform. Higher CSF-tau and CSF-ubiquitin levels were also associated with increasing degree of cortical and central brain atrophy as measured by computerized tomography. The relationships between CSF-tau and severity of dementia and to brain atrophy suggest that CSF-tau may be used as a measure of neuronal/axonal degeneration in patients with dementia. We have previously shown a marked increase in both CSF-tau and CSF-ubiquitin in younger patients with AD and VAD. The less pronounced increase in CSF-tau and the lack of difference in CSF-ubiquitin in older patients suggest that the severity of the degenerative process is less in older than in younger demented patients.

Aged↗