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Biomedical subjects

K Blennow

Publications and source records attributed to K Blennow.

At least 163 records · Page 9Linked to original sources
PubMed1992

Sulfatide as a biochemical marker in cerebrospinal fluid of patients with vascular dementia.

The myelin-associated glycosphingolipid sulfatide in cerebrospinal fluid (CSF) was investigated in 20 patients with vascular dementia (VAD), 43 with Alzheimer's disease (AD) and 20 age-matched controls. The sulfatide concentration in the VAD group (307 +/- 118 nmol/l) was significantly (p less than 0.0001) higher than that in controls (145 +/- 86 nmol/l) and the AD group (178 +/- 79 nmol/l). Among the VAD patients, 8/20 had a significantly increased concentration of sulfatide (greater than mean + 2 S.D.), as compared with controls, while only 2/43 of the AD patients had a sulfatide concentration above this level. It is suggested that the elevated concentration of sulfatide in CSF from VAD patients reflects demyelination. Furthermore, sulfatide determinations, when combined with clinical findings, may be of diagnostic value, for discriminating between VAD and AD.

Aged↗
PubMed1992

Vitamin B12 in CSF: reduced CSF/serum B12 ratio in demented men.

Vitamin B12 concentrations were determined in serum and cerebrospinal fluid (CSF) of 32 controls and 102 patients with dementia. The dementias were classified as Alzheimer's disease (AD), senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID). A substantial number of patients (n = 42) could not be assigned to any of these diagnostic groups, as their dementias were of non-AD/SDAT and non-MID types. They were instead assigned to a group called non ultra descriptum (NUD). CSF B12 correlated significantly with serum B12. There were no statistically significant differences in serum B12 levels between the groups. Although with considerable overlap, CSF B12 concentrations and CSF/serum B12 ratios were significantly lower in the NUD group than in the control group. The NUD group had significantly lower CSF/serum B12 ratios than the group of patients with AD/SDAT. There was significant male predominance in the group of demented patients that had low CSF/serum B12 ratios outside the bivariate reference region. CSF and serum B12 levels appear insufficient as measures of the true brain vitamin B12 status. It may be a more dynamic approach to use the CSF/serum B12 ratio as an indication of transport function across the blood brain barrier, and possibly also across the CSF brain cell barrier.

Aged↗
PubMed1992

Differences in cerebrospinal fluid gangliosides between "probable Alzheimer's disease" and normal aging.

The four major brain gangliosides, GM1, GD1a, GD1b, and GT1b, were determined in cerebrospinal fluid (CSF) of 43 patients with "probable Alzheimer's disease (AD)" and 40 healthy controls without psychiatric or neurological disorders. The total concentration of the four gangliosides did not differ significantly between "probable AD" group (116 +/- 58 nmol/L) and controls (92 +/- 31 nmol/L), but the proportion between the gangliosides was changed. In the "probable AD" group compared with the age-matched control group, there was an increase in both the GM1 (22.6 +/- 9.3% vs 12.6 +/- 4.1%; p < 0.0001) and GD1a (32.1 +/- 9.8% vs 23.3 +/- 5.7%; p < 0.0005) proportion, and a decrease in the GD1b (20.0 +/- 6.6% vs 23.8 +/- 6.0%; p < 0.05) and GT1b (25.3 +/- 7.9 vs 40.3 +/- 9.3%; p < 0.0001) proportion. The proportion of GM1 showed a positive correlation with age in the control group (r = 0.45; p < 0.01), but a negative correlation with age in the "probable AD" group (r = -0.37; p < 0.05). Thus, although the increase in proportion GM1 in the "probable AD" group was preferentially found in younger "probable AD" patients, it was not caused by age differences. While the pathogenetic mechanism for these changes in CSF-gangliosides in "probable AD" remains to be established, it may reflect the degeneration of nerve cells and synapses.

Adolescent↗
PubMed1991

Quantitative changes in the amyloid beta A4 precursor protein in Alzheimer cerebrospinal fluid.

The major three secretory isoforms of Alzheimer beta A4 amyloid precursor protein (APP) were quantified in cerebrospinal fluid (CSF) using (1) a newly developed enzyme-linked immunosorbent assay (ELISA) and (2) densitometric analysis of CSF Western blots. The protease inhibitor-containing APP751/770 isoforms represented an average of 10.5% of total APP in CSF of patients with Alzheimer's disease (AD, n = 22), multi-infarct dementia (MID, n = 5) and normal controls (n = 10). APP levels in CSF did not depend on total CSF protein. Both findings are inconsistent with a hematogeneous origin of APP in CSF and suggest an intracerebral source. Total APP, APP695 and APP751/770 were significantly decreased in the AD and in the MID groups, but were not correlated to the ages of patients or controls.

Aged↗
PubMed1991

Gangliosides in cerebrospinal fluid in 'probable Alzheimer's disease'.

The concentrations of the four major brain gangliosides--GM1, GD1a, GD1b, and GT1b--were determined in cerebrospinal fluid from 43 patients with "probable Alzheimer's disease" and 19 healthy controls. Alzheimer's disease was divided into type I (with the memory disturbances and predominant cortical parietal symptoms that are characteristic of Alzheimer's disease) and type II (with general cognitive and mild confusional symptoms, with or without only mild parietal symptoms). The GM, concentration was significantly higher in patients with Alzheimer's disease type I than in those with Alzheimer's disease type II and age-matched controls, but did not differ significantly between patients with Alzheimer's type II and age-matched controls. As gangliosides are enriched in nerve cell membranes, preferentially in synapses, the findings suggest more severe degeneration of cortical nerve cells in patients with Alzheimer's disease type I than in those with Alzheimer's disease type II.

Aged↗
PubMed1991

Pathogenetic basis of vascular dementia.

Vascular dementia (VAD) was studied with reference to pathogenetic aspects, especially the importance of brain infarcts. A VAD diagnosis was chosen when the patients showed dementia in combination with transitory ischemic attacks (TIA), stroke episodes, or other pronounced vascular diseases judged to be causally related to the dementia. Computed tomography (CT) white matter lesions were shown to occur frequently (85%); a pronounced decrease in myelin lipids was common in subcortical white matter; a fronto-subcortical symptom complex was the prevailing clinical pattern; and an overall increased albumin ratio without relation to TIA/stroke was noted, indicating blood-brain barrier (BBB) dysfunction. When infarcts were present, they appeared to be endpoint manifestations of the vascular pathology rather than the cause of the disease. Today, thromboembolism with multiple cerebral infarcts is considered more or less the only pathogenetic substrate of VAD, with multi-infarct dementia (MID) as its clinical counterpart. Our findings suggest that subcortical white matter changes are another important VAD substrate.

Aged↗
PubMed1991

White-matter lesions on CT in Alzheimer patients: relation to clinical symptomatology and vascular factors.

Fifty-four patients with Alzheimer's disease (AD) were examined for white-matter lesions (WMLs) using computerized tomography. WMLs were more frequent in late-onset AD (LAD) (26/34-76%) than in early-onset AD (EAD) (5/20-25%) (p less than 0.0001), in AD without parietal predominance (10/11-91%) (p less than 0.005) than in AD with parietal predominance (5/15-33%), and in AD with confusional symptoms (11/12-92%) than in AD without confusional symptoms (4/14-29%) (p less than 0.001). The supine systolic blood pressure was higher in AD with WMLs (151 +/- 20) than in AD without WML (139 +/- 22) (p less than 0.05). AD patients with WMLs, but not those without WMLs, had a higher mean albumin ratio (7.5 +/- 2.7) than healthy controls (5.7 +/- 2.1) (p +/- 0.005). The finding of less focal (= less parietal) symptomatology in AD with WMLs than without WMLs suggests clinical significance of WMLs in AD, while the relations between blood pressure, BBB function and WMLs support the hypothesis of a vascular pathogenesis.

Aged↗
PubMed1990

Intrathecal synthesis of immunoglobulins in patients with Alzheimer's disease.

Serum and cerebrospinal fluid (CSF) of 45 patients with Alzheimer's disease (AD) and 24 healthy controls were examined in order to investigate the possibility of an intrathecal synthesis of immunoglobulins in AD. The group of AD patients showed higher IgG and IgM indices than the control group. Five (11%) AD patients had an intrathecal IgG synthesis and 7 (15%) an intrathecal IgM synthesis. In total, 12 (26%) AD patients had an intrathecal immunoglobulin synthesis, while there was none among the controls. This finding supports the hypothesis that immunological mechanisms may play a role in the etiology and/or pathogenesis of Alzheimer's disease, at least in a subgroup of patients.

Aged↗
PubMed1990

Parenteral administration of GM1 ganglioside to presenile Alzheimer patients.

The pharmacokinetic parameters of GM1 ganglioside were examined in 16 patients (mean age 64 +/- 5 years) with Alzheimer's disease. The ganglioside was given intramuscularly and subcutaneously. The maximum GM1 blood level was reached after 48-72 h, the subcutaneous route leading to the highest blood levels, but the individual variability was relatively large. When 100 mg GM1 ganglioside was given daily for a week, maximum serum values of 15 to 20 mumol/l were found in 3 patients. The elimination half-life from serum was 60-75 h.

Aged↗
PubMed1990

Intrathecal synthesis of immunoglobulin G in vascular dementia.

Serum and CSF from 53 vascular dementia (VD) patients and 50 controls were analysed to investigate the possibility of an intrathecal synthesis of IgG, defined as an elevated IgG index (greater than or equal to 7) and/or presence of oligoclonal IgG in cerebrospinal fluid (CSF), but not in serum. Five (9%) patients and no controls exhibited an intrathecal synthesis of IgG. The IgG index increased with the degree of dementia (p less than 0.05). It was positively related to presence/absence of hypertension (p less than 0.05) and correlated positively with diastolic blood pressure (p less than 0.05). The findings suggest that immunological factors might be involved in the pathogenesis of VD.

Aged↗
PubMed1990

Blood brain barrier function in vascular dementia.

To investigate blood-brain barrier (BBB) function measured as an albumin ratio (cerebrospinal fluid/serum) in vascular dementia (VD) samples from 53 patients and 30 healthy controls were analysed. The VD group showed a higher mean albumin ratio than controls (8.5 +/- 3.8 and 5.7 +/- 2.1, respectively). The albumin ratio did not correlate significantly with age, nor with individual clinical vascular factors. The results of the present study suggest that the altered BBB might be a consequence of small vessel disorder rather than evidence of infarcts.

Aged↗
PubMed1990

Blood-brain barrier disturbance in patients with Alzheimer's disease is related to vascular factors.

To investigate the blood-brain barrier (BBB function), serum and cerebrospinal fluid (CSF) from 118 patients with Alzheimer's disease (AD) and 50 healthy controls was analyzed with regard to albumin concentrations. For the AD group, clinical vascular factors were also recorded. The CSF/serum albumin ratio was used as a measure of BBB function. When compared with controls, the AD group showed a higher mean albumin ratio, indicating a decline in BBB function. However, no significant reduction in BBB function was found in AD patients without vascular factors. These findings support the hypothesis that BBB disturbance is related to vascular factors, coexisting with AD. In the control group, no significant correlation between age and albumin ratio was found, which suggests that aging per se is not primarily associated with a decline in BBB function. The present study provides evidence in favour of the conclusion that a reduced BBB function is related neither to AD nor to aging, but to clinical vascular factors.

Aged↗
PubMed1990

Confusional symptomatology distinguishes early- and late-onset Alzheimer's disease.

Symptoms of confusion were examined in 75 patients with Alzheimer's disease (AD). Mild confusion was found in 20, and mode-rate/severe confusion in 8 patients. Confusion was more frequent in the late-onset (26/44-59%) than in the early-onset AD group (2/31-6%) (p less than 0.0001), and patients with confusion were older (p less than 0.0001) than those without confusion. The frequency of confusion was higher in patients with ischemic heart disease (13/28-46%) than in patients without this vascular factor (10/47-21%) (p less than 0.05). An inverse relation was found between confusional symptomatology and parietal-lobe symptoms. The findings in this study suggest that a subgroup of AD patients, fulfilling the NINCDS-ADRDA criteria for probable AD, is characterized by a clinical picture of mild confusional symptomatology together with no or mild parietal-lobe symptomatology, higher age and higher frequency of ischemic heart disease. This group contrasts with the other subgroup of pure AD, which is characterized by a clinical picture of marked parietal-lobe symptomatology, almost no confusional symptomatology, lower age and lower frequency of ischemic heart disease.

Aged↗
PubMed1990

Intra-blood-brain-barrier synthesis of immunoglobulins in patients with dementia of the Alzheimer type.

Serum and cerebrospinal fluid (CSF) of 56 patients with dementia of the Alzheimer type (DAT) and 33 healthy controls were examined in order to investigate intra-blood-brain-barrier (intra-BBB) synthesis of immunoglobulins. Intra-BBB immunoglobulin G (IgG) synthesis was defined as an elevated IgG index (greater than 0.7) and/or presence of oligoclonal IgG in CSF but not in serum on isoelectric focusing, and intra-BBB immunoglobulin M (IgM) synthesis as an elevated IgM index (greater than 0.06). In total, 10 (18%) DAT patients displayed an intra-BBB immunoglobulin synthesis--five (9%) an IgG and five (9%) an IgM synthesis--but none among the controls. Also, the DAT patient group showed higher mean IgG and IgM indexes than the control group. These findings support the hypothesis that immunological mechanisms may play a role in the etiology and/or pathogenesis of Alzheimer disease, at least in a subgroup of patients.

Aged↗
PubMed1989

Monoamine metabolites in cerebrospinal fluid and behavioral ratings in patients with early and late onset of Alzheimer dementia.

Patients with Alzheimer disease (AD, onset less than 65 years of age, n = 13) and senile dementia of the Alzheimer type (SDAT, onset greater than or equal to 65 years of age, n = 28) were investigated for cerebrospinal fluid (CSF) content of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxy-phenylglycol (MHPG) and compared with a group of controls (n = 26). A geriatric rating scale, the Gottfries-Bråne-Steen scale, was used to assess impairment of motor performance, intellectual and emotional functioning, and symptoms common in dementia disorders. The HVA levels in CSF were significantly lower in the AD group than in the SDAT group and controls. MHPG was slightly but significantly increased in the SDAT group when compared with the controls. The HVA and 5-HIAA concentrations were correlated negatively with impairment of motor performance in the SDAT group; 5-HIAA correlated positively with impaired performance in the AD group; and 5-HIAA/HVA ratios were correlated positively with the performance variables. HVA correlated significantly and negatively with "impaired wakefulness" and "inability to increase tempo" in the SDAT group. 5-HIAA and the ratio 5-HIAA/HVA correlated significantly and positively with some items measuring intellectual and emotional impairment. In the AD group, "anxiety" and "fear-panic" correlated positively with 5-HIAA and "restlessness" with MHPG. The data indicate qualitative differences in the CSF monoamine pattern between AD and SDAT.

Aged↗
PubMed1989

White matter low attenuation on computed tomography in Alzheimer's disease and vascular dementia--diagnostic and pathogenetic aspects.

Demented patients with early-onset Alzheimer's disease (AD) (n = 17), late-onset Alzheimer's disease (n = 30) and vascular dementia (VD) (n = 20) were studied with computed tomography of the brain. Semiquantitative evaluation of white matter low attenuation (WMLA) and central and cortical atrophy was performed without knowledge of the clinical diagnosis. In early onset AD there was almost complete absence of WMLA and central atrophy compared with the other groups, which showed moderate to severe changes. This suggests that early-onset AD should be separated from the late-onset form. The increased systolic blood pressure found in the WMLA group supports the opinion that WMLA has a vascular origin. The high percentage of WMLA in VD and late-onset AD indicates that subcortical factors have to be considered in the pathogenesis of these disorders.

Aged↗
PubMedDate not supplied

Identification of proteins in a human pleural exudate using two-dimensional preparative liquid-phase electrophoresis and matrix-assisted laser desorption/ionization mass spectrometry.

Pleural effusion may occur in patients suffering from physical trauma or systemic disorders such as infection, inflammation, or cancer. In order to investigate proteins in a pleural exudate from a patient with severe pneumonia, we used a strategy that combined preparative two-dimensional liquid-phase electrophoresis (2-D LPE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and Western blotting. Preparative 2-D LPE is based on the same principles as analytical 2-D gel electrophoresis, except that the proteins remain in liquid phase during the entire procedure. In the first dimension, liquid-phase isoelectric focusing allows for the enrichment of proteins in liquid fractions. In the Rotofor cell, large volumes (up to 55 mL) and protein amounts (up to 1-2 g) can be loaded. Several low abundance proteins, cystatin C, haptoglobin, transthyretin, beta2-microglobulin, and transferrin, were detected after liquid-phase isoelectric focusing, through Western blotting analysis, in a pleural exudate (by definition, >25 g/L total protein). Direct MALDI-TOF-MS analysis of proteins in a Rotofor fraction is demonstrated as well. MALDI-TOF-MS analysis of a tryptic digest of a continuous elution sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) fraction confirmed the presence of cystatin C. By applying 2-D LPE, MALDI-TOF-MS, and Western blotting to the analysis of this pleural exudate, we were able to confirm the identity of proteins of potential diagnostic value. Our findings serve to illustrate the usefulness of this combination of methods in the analysis of pathological fluids.

Blotting, Western↗