Increased aspartate aminotransferase activity in cerebrospinal fluid and Alzheimer's disease.
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Aged↗
Biomedical subjects
T Pirttilä
Publications and source records attributed to T Pirttilä.
Longitudinal study of cerebrospinal fluid amyloid proteins and apolipoprotein E in patients with probable Alzheimer's disease.
Levels of soluble amyloid beta protein (sAbeta), amyloid beta precursor protein (APP) and apolipoprotein E (apoE) were examined in cerebrospinal fluid (CSF) obtained twice, at baseline and after 3-year follow-up, from 25 patients with probable Alzheimer's disease (AD). Levels of sAbeta and apoE from patients with the apoE4 allele decreased with time, whereas the levels were similar in patients without apoE4 allele. Changes of sAbeta and apoE concentrations correlated significantly with those of mini-mental state examination (MMSE) scores. Levels of sAbeta did not change with time in patients with mild dementia, whereas they decreased significantly in patients with moderate dementia. ApoE concentrations decreased in both groups whereas APP levels were similar. We conclude that measurements of CSF sAbeta and apoE levels may be helpful in monitoring progression of the disease.
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Aggregation of amyloid beta-protein as function of age and apolipoprotein E in normal and Alzheimer's serum.
We compared the effect of serum from (a) 26 Alzheimer's disease (AD) patients and 22 age-matched non-demented controls (CO) with apolipoprotein E 4/4, 3/3 or 3/2 phenotypes, and (b) 17 normal young (aged 15-41 years) and 21 normal elderly (aged 64-83 years) people on in vitro aggregation of synthetic amyloid beta-protein (A beta) 1-40 by Thioflavin T fluorescence spectroscopy. A beta 1-40 aggregation in presence of serum from the normal elderly group was significantly higher as compared to the normal young group (correlation coefficient between age and A beta aggregation=0.73). However, no difference in A beta aggregation was observed in the presence of serum from AD patients and non-demented controls. There was a positive correlation between serum apo E concentrations and A beta aggregation, while there was no significant difference between different apo E phenotypes. The correlation coefficient in the AD 4/4 (0.65) was higher than the CO 4/4 group (0.04), while it was lower in the AD 3/3 group (-0.12) than in the CO 3/3 (0.39) group. These results suggest that the apo E4 allele alone may not be responsible for A beta fibril formation in AD; other factors may be involved in increasing risk for AD pathogenesis in those having the apo E4 allele. The severity of dementia and serum albumin levels also did not correlate with A beta aggregation. We propose that the age of an individual may be an important factor in determining the degree of A beta aggregation/fibrillization, and that mechanism of sequestration of A beta in serum may not be defective in AD.
Adolescent↗
Unidentified antioxidant defences of human plasma in immobilized patients: a possible relation to basic metabolic rate.
Plasma total peroxyl radical scavenging capacity was studied in terminal patients who were chronically immobilized because of an acute (stroke) or chronic neurodegenerative disease (Alzheimer's disease). A luminometric assay was used to measure total antioxidant capacity (TRAP). The immobilized patients showed significant decrease in TRAP primarily because of a decrease in the concentration of unknown antioxidants. Our results suggest that human plasma may contain unknown antioxidants, the regulation of which could be related to the basic metabolic rate.
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Effect of cerebrospinal fluid from normal and Alzheimer's patients with different apolipoprotein E phenotypes on in vitro aggregation of amyloid beta-protein.
We examined the effect of cerebrospinal fluid (CSF) from 23 Alzheimer's disease (AD) patients and 22 age-matched non-demented controls with apolipoprotein E4/4, 3/3, or 3/2 phenotypes on in vitro aggregation of amyloid beta-protein (A beta) 1-40 by Thioflavin T fluorescence spectroscopy. CSF from both AD and control groups inhibited A beta aggregation, as compared to that of phosphate buffered saline, in agreement with an earlier report (Wisniewski et al., 1993). However, there was significantly less aggregation of A beta in presence of CSF from AD than that from non-demented controls. The presence of CSF from controls with apoE3/3 phenotype resulted in higher A beta aggregation as compared to other phenotypes. There was a positive correlation between CSF apoE concentrations and A beta aggregation; whereas age, CSF soluble A beta levels or severity of dementia did not correlate with A beta aggregation. These results suggest that mechanism of sequestration of A beta in CSF may not be defective in AD. Amyloid formation in AD may be impact of altered balance of other factors such as amyloid-associated proteins/extracellular matrix components that can immobilize A beta in the brain, and promote its fibrillogenesis in AD.
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Apolipoprotein E (apoE) levels in brains from Alzheimer disease patients and controls.
We measured apolipoprotein E (apoE) level in neutral and acidic pH extracts of the frontal, temporal and cerebellar cortices from patients with definite Alzheimer's disease (AD) and controls, and analyzed the relationship among apoE levels, clinical and neuropathological findings, and apoE genotype. Our data showed that the levels varied in different brain regions being lowest in the frontal cortex and highest in the cerebellum in Ad brains. ApoE levels in neutral pH extracts from the frontal cortex from AD patients were significantly lower than those of controls, and correlated negatively with the number of neurofibrillary tangles. ApoE genotype was not associated with the levels of apoE. There was no correlation between apoE levels and amyloid load or synaptophysin-immunoreactivity in the brain. We conclude that apoE levels are not increased in AD brains. However, apoE levels vary in different brain regions, and local factors related to the synthesis and metabolism of apoE may be crucial in the pathogenesis of AD.
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Cerebrospinal fluid concentrations of soluble amyloid beta-protein and apolipoprotein E in patients with Alzheimer's disease: correlations with amyloid load in the brain.
OBJECTIVE: To compare soluble amyloid beta-protein and apolipoprotein E levels in cerebrospinal fluid (CSF) and brain extracts from patients with definite Alzheimer's disease. SETTING: University medical center. PATIENTS: Nineteen patients with definite Alzheimer's disease. MAIN OUTCOME MEASURES: Soluble amyloid beta-protein and apolipoprotein E levels in CSF, in neutral and low-pH brain extracts, and in formic acid-treated sections of the frontal, temporal, and cerebellar cortices, measured using enzyme-linked immunosorbent assay. RESULTS: Soluble amyloid beta-protein and apolipoprotein E levels in CSF were significantly lower in patients with congophilic angiopathy than in those without angiopathy. The levels did not correlate with the number of amyloid plaques in the neocortex. There was, however, a tendency toward an inverse correlation between the amount of amyloid beta-protein in the frontal cortex extracts and the soluble amyloid beta-protein level in CSF. CONCLUSION: Soluble amyloid beta-protein levels in CSF may reflect amyloid accumulation in brain blood vessels.
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The frequency of apolipoprotein E4 allele is not increased in patients with probable vascular dementia.
We used the NINDS-AIREN criteria to diagnose vascular dementia (VD), and compared apolipoprotein E (apoE) allele frequencies and apoE concentrations in serum and cerebrospinal fluid (CSF) between patients with possible (n = 19) and probable (n = 33) VD and controls (n = 105). There was no difference in apoE4 frequency between patients with probable VD and controls. Serum and CSF apoE concentrations did not differ between VD patients and controls. Our results suggest that apoE plays no role in the development of VD.
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Apolipoprotein E (apoE) polymorphism and its influence on ApoE concentrations in the cerebrospinal fluid in Finnish patients with Alzheimer's disease.
The apoE phenotype of 83 patients with probable Alzheimer's disease (AD) and of 164 non-demented controls was determined by isoelectric focusing and Western blotting. The proportion of the epsilon 4 allele was 0.548 in AD and 0.202 in controls (P < 0.0001). The effect was seen in both early-onset and late-onset AD patients. The risk of AD in epsilon 4 homozygotes was 18-fold greater than in individuals without the epsilon 4 allele. ApoE concentrations were measured in serum and cerebrospinal fluid (CSF) from a subgroup of patients with AD (n = 72) and controls (n = 84) by a sandwich enzyme-linked immunosorbent assay. Although serum apoE concentrations were lower in individuals with the epsilon 4 allele than in those without the epsilon 4 allele, CSF apoE concentrations did not vary in different phenotype groups. However, CSF apoE levels were lower in AD patients than in controls. We conclude that the inheritance of the epsilon 4 allele of apoE is a risk factor for AD in the Finnish population.
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CSF oligoclonal bands, MRI, and the diagnosis of multiple sclerosis.
In this retrospective study, the results from investigations (MRI, evoked potentials, alkaline oligoclonal bands [OBs] in CSF) in 94 patients with clinical suspicion of demyelinative disease were evaluated to assess their impact on diagnosis. Forty-three patients were diagnosed as having definite MS, 10 probable MS, and 9 possible MS. MRI findings strongly suggestive of MS were evident in 52/62 (84%) patients, while 47/62 (76%) patients demonstrated OBs in their CSF. In 63% of patients both abnormalities were present. Patients with no OBs in their CSF were on the average older, were more often male, had experienced their first symptoms at a later age, and suffered more often from the chronic-progressive form of the disease than those with a positive CSF finding.
Adult↗
[Alzheimer's disease and the association of genetic polymorphism of apolipoprotein E and liquor beta protein in Finns].
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Soluble amyloid beta-protein in the cerebrospinal fluid from patients with Alzheimer's disease, vascular dementia and controls.
Cerebrospinal fluid (CSF) soluble amyloid beta-protein (sA beta) concentrations from 69 patients with Alzheimer's disease (AD), 23 patients with vascular dementia (VD), and 76 non-demented controls were measured by a sandwich enzyme linked immunosorbent assay using two monoclonal antibodies (4G8 and 6E10) specific for A beta. sA beta concentrations were lower in CSF from patients with AD or VD compared to those in controls. CSF sA beta concentrations did not correlate with the Mini-Mental State Examination scores in patients with AD. VD patients with moderate to severe dementia had lower CSF sA beta concentrations than those with mild dementia. Because a considerable overlap of CSF sA beta levels existed between AD and control groups, the assay is not useful as a diagnostic test for AD.
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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↗
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.
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Effect of advanced brain atrophy and vitamin deficiency on cognitive functions in non-demented subjects.
The relationship between the cognitive functions, structural changes of the brain and vitamin levels was evaluated in 36 non-demented subjects with advanced brain atrophy, and 57 age- and sex-matched healthy controls. In the control subjects ageing was associated with mild decline of cognitive skills, but the cognitive changes were not linked to the structural changes of the brain. In contrast, advanced brain atrophy and vitamin deficiency was related to the decline of complex cognitive functions in the atrophy group. Our results indicate that there are limits of normal age-related changes of the brain structure, and advanced brain atrophy on CT scans increase the probability of mild deficits of the cognitive skills.
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Effects of recombinant alpha-2b-interferon therapy in patients with progressive MS.
The effects of systemic recombinant interferon-alpha-2b were studied in 6 carefully selected patients with progressive multiple sclerosis. 3.0 million IU were given as daily subcutaneous injections for 6 months, 5 patients showed worsening disability, and in 4 of them new or enlarged lesions were detected in MRI. In one patient no change in disability was found; his MRI showed regressed changes. The mean progression index during the treatment was significantly higher (p < 0.02) than during the previous 2 to 3 years' period of continuous progression. The frequency of peripheral blood natural killer (CD16+) cells declined significantly 3 months during the treatment, but returned to the pretreatment values after termination the treatment. An increase of intrathecal IgG synthesis and oligoclonal bands was demonstrated in 4 and 3 patients, respectively. Our experience suggests that long-term recombinant IFN-alpha-2b treatment may activate the immunological process of MS.
Adult↗
Brain atrophy in neurodegenerative diseases. Quantitative and qualitative CT analysis.
A quantitative and qualitative analysis was done of 187 CT examinations in 59 healthy subjects and 128 patients with various neurodegenerative diseases. The rates of agreement between quantitative measurements and the qualitative grading by two observers were 76.7% for the evaluation of lateral ventricular size and 66.3% for the assessment of sulcal size. Increase in the width of the 3rd ventricle, in the bi-caudate span, and in the area of the lateral ventricles reflected a pathologic enlargement of the ventricles. The profile of ventricular dilatation in dementia patients was different from that of other patients with brain atrophy. However, the quantitative measurement of brain atrophy by a computer-based method did not increase the differential diagnostic accuracy among dementia patients. The results stress the importance of the selection of valid measures in the evaluation of structural changes of the brain. We suggest the use of reference scans for improving the reliability of the visual evaluation.
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