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S Sorbi

Publications and source records attributed to S Sorbi.

At least 109 records · Page 6Linked to original sources
PubMed1992

Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14.

Familial Alzheimer's disease (FAD) has been shown to be genetically heterogeneous, with a very small proportion of early onset pedigrees being associated with mutations in the amyloid precursor protein (APP) gene on chromosome 21, and some late onset pedigrees showing associations with markers on chromosome 19. We now provide evidence for a major early onset FAD locus on the long arm of chromosome 14 near the markers D14S43 and D14S53 (multipoint lod score z = 23.4) and suggest that the inheritance of FAD may be more complex than had initially been suspected.

Aged↗
PubMed1991

The first Alzheimer disease case: a metachromatic leukodystrophy?

A reconsideration of the original report of Alzheimer and of the description of case 1 by Perusini in 1908, published in 1910, suggests that they were describing the same case. Both the temporal evidence and the clinical description make this conclusion inescapable. The histopathology of this first case shows some features that are not characteristic of the histological pattern of the modern Alzheimer, namely demyelination of the central white matter and metachromatic deposits in the spinal cord.

Alzheimer Disease↗
PubMed1990

Occurrence of transketolase abnormalities in extracts of foreskin fibroblasts from patients with Alzheimer's disease.

Foreskin fibroblast cell lines from healthy subjects and patients with Alzheimer's disease or other neurological disorders have been analyzed for transketolase, by means of isoelectrofocusing and specific immunostaining. The enzyme profile in 70% of Alzheimer cell cultures exhibits alterations which are not encountered in controls and in other neurological diseases examined. Enzyme abnormalities most frequently observed were the appearance of new transketolase forms having unusually high alkaline pI. Experiments carried out with intact cells and with cell extracts treated with and without phenylmethyl-sulphonyl fluoride, suggest that the peculiar transketolase abnormalities observed in Alzheimer fibroblasts are due to enhanced proteolysis occurring in these cells rather than to intrinsic enzyme lability.

Alzheimer Disease↗
PubMed1990

Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder.

Alzheimer's disease, a fatal neurodegenerative disorder of unknown aetiology, is usually considered to be a single disorder because of the general uniformity of the disease phenotype. Two recent genetic linkage studies revealed co-segregation of familial Alzheimer disease with the D21S1/S11 and D21S16 loci on chromosome 21. But two other studies, one of predominantly multiplex kindreds with a late age-of-onset, the other of a cadre of kindreds with a unique Volga German ethnic origin, found absence of linkage at least to D21S1/S11. So far it has not been possible to discern whether these conflicting reports reflect aetiological heterogeneity, differences in methods of pedigree selection, effects of confounding variables in the analysis (for example, diagnostic errors, assortative matings), or true non-replication. To resolve this issue, we have now examined the inheritance of five polymorphic DNA markers from the proximal long arm of chromosome 21 in a large unselected series of pedigrees with familial Alzheimer's disease. Our data suggest that Alzheimer's disease is not a single entity, but rather results from genetic defects on chromosome 21 and from other genetic or nongenetic factors.

Alzheimer Disease↗
PubMed1990

Altered hexokinase activity in skin cultured fibroblasts and leukocytes from Alzheimer's disease patients.

Changes in the activity of brain glycolytic enzymes have been reported in Alzheimer's dementia. In this paper we studied the activity of the rate-limiting glycolytic enzymes, namely phosphofructokinase, lactate dehydrogenase and hexokinase in skin cultured fibroblasts and leukocytes from familial and sporadic Alzheimer's disease patients and unaffected relatives. Phosphofructokinase and lactate dehydrogenase activities were similar in all groups studied. The activity of hexokinase was reduced in some patients with the familial dominant form of Alzheimer's disease whilst it was normal in sporadic cases. These results suggest that Alzheimer's disease may be an heterogeneous disorder and that a modification on the catalytic activity of hexokinase may play a role in the pathogenesis of the disease in at least a subgroup of patients.

Alzheimer Disease↗
PubMed1990

Changes in Na+,K(+)-ATPase, Ca2(+)-ATPase and some soluble enzymes related to energy metabolism in brains of patients with Alzheimer's disease.

Hexokinase, lactate dehydrogenase, acylphosphatase, (Na+,K+)-ATPase and Ca2(+)-ATPase of selected areas from postmortem Alzheimer's disease brains were studied. Hexokinase and lactate dehydrogenase were significantly changed in all the examined subcortical nuclei. (Na+,K+)-ATPase activity was altered in several areas of Alzheimer's disease brains. No changes in Ca2(+)-ATPase and acylphosphatase were observed. The main alterations of the assayed enzymes were observed in subcortical areas but not in cortical areas of Alzheimer's disease brains.

Aged↗
PubMed1990

Changes in pyruvate dehydrogenase complex (PDHc) activity and [3H]QNB-receptor binding in rat brain subsequent to intracerebroventricular injection of bromopyruvate.

Pyruvate dehydrogenase complex (PDHc), a link between carbohydrate and acetylcholine metabolism, is a regulatory enzyme for glucose and neurotransmitter metabolism in the brain and is reduced in Alzheimer-diseased brain. To study functional consequences of an inhibition of PDHc on muscarinic receptor binding, bromopyruvate, a suicide inhibitor od PDHc, was injected intracerebroventricularly (icv) in rats. Bromopyruvate caused a reduction of PDHc activity in the 3 brain regions examined, however, reaching significance only in the cerebral cortex and the hippocampus and not in the striatum, 24 h after injection. 3, 6, and 12 weeks later, there was a normalization or transiently increased activity, respectively, of PDHc in these brain regions. No changes in concentrations of energy-rich phosphates could be demonstrated in the cerebral cortex 12 weeks after brompyruvate injection. The number of muscarinic receptors was significantly reduced in the cerebral cortex 12 weeks after injection. The data indicate that a transient reduction of brain PDHc activity in vivo is associated with a long-lasting reduction in muscarinic cholinergic receptors. Because comparable changes of PDHc and muscarinic receptors are found in dementia of Alzhemier type, the model of bromopyruvate inhibition of PDHc in rats is suggested to be useful for experimental dementia research.

Alzheimer Disease↗
PubMed1990

Rating of the lesions in senile dementia of the Alzheimer type: concordance between laboratories. A European multicenter study under the auspices of EURAGE.

The study reported was intended to compare the impressions and analyses of investigators from 11 different laboratories on 2 slides, each from 6 cases with varying quantities of neuropathological change of the type found in Alzheimer's disease and normal ageing. The material came from 6 selected female patients over 75 years of age all of whom had been examined in detail and assessed by the Blessed Test Score. Two were severely demented, 2 mildly demented and 2 were considered to be normal. Unstained paraffin-embedded slides were sent to the investigators, the choice of the staining techniques being left to each laboratory. A quantitative evaluation of the changes was requested in 2 specified areas of the hippocampus and in the first temporal gyrus. Subjective scores of severity and a final guess about the pre mortem intellectual status (demented or not) were asked. The 11 replies were analyzed. A total of 14 different staining techniques were used. Absolute values of density differed much from one investigator to another, for senile plaques as well as for neurofibrillary tangles. Statistical analysis showed that concordance might be improved by the use of corrective factors which would standardize the scales of measurement. The ranking of the slides in increasing order of severity was in good agreement for 9 out of 11 observers concerning the neurofibrillary tangles and 3 out of 9 observers concerning the senile plaques. The correlation between the intellectual status and the density of lesions was higher for neurofibrillary tangles than for senile plaques. The subjective scores were in better agreement for the severely affected cases than for the mildly affected ones. The lowest correlation with intellectual deficit was obtained with the quantitative scores which took into account only the senile plaques or only the hippocampal lesions. The highest correlation coefficients were obtained with the subjective scores. The observers guessed correctly the intellectual status of the 2 most affected cases and often disagreed for the intermediate and normal cases. Neuropathology is mandatory for the diagnosis of definite Alzheimer's disease. Quantitative assessment is useful in cases with few lesions and light dementia but the neuropathological diagnostic procedure has to be more strictly standardized before quantitative histopathological criteria can be reliably transferred from one laboratory to another, especially when mildly affected cases are involved. Concordance seems presently easier to obtain by ranking the lesions and the cases in increasing order of severity than by using quantitative values of density.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1989

Abnormalities of mitochondrial enzymes in hereditary ataxias.

The activity of 7 mitochondrial enzymes, fumarase, NAD-malate dehydrogenase (MDH), citrate synthase (CS), valine dehydrogenase (VDH), succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), pyruvate dehydrogenase complex (PDHC) has been measured in platelet preparations from patients affected by Friedreich's ataxia (FA), dominant and non-dominant olivopontocerebellar atrophy (DOPCA, NDOPCA) and normal individuals. Significant decreases of GDH (P less than 0.01), PDHC (P less than 0.01), VDH (P less than 0.05) and SDH (P less than 0.05) activities were observed in FA patients. Significant decreases of GDH (P less than 0.01), PDHC (P less than 0.01), VDH (P less than 0.05), SDH (P less than 0.05) and CS (P less than 0.05) activities were Observed in ND-OPCA patients, whereas in DOPCA patients only GDH activity was significantly (P less than 0.05) decreased. In 8 of 10 patients with FA and in all patients with NDOPCA the activity of one or more of 4 enzymes, i.e. GDH, VDH, SDH, PDHC, was lower than the lowest of control values. Four of 6 patients with DOPCA had GDH activity lower than the lowest of control values. These results indicate that abnormalities of mitochondrial metabolism is a constant element in hereditary ataxia and suggest that the alteration primary leading to the different types of ataxias should be related to mitochondrial oxidative metabolism, at least at a regulatory level.

Adolescent↗
PubMed1988

Lack of efficacy of phosphatidylcholine in ataxias.

We gave phosphatidylcholine orally at a daily dosage of 9 grams for 4 years to 20 subjects with Friedreich's ataxia (FA) and 24 with olivopontocerebellar atrophy (OPCA). There was no clinical improvement during the follow-up compared with 12 ataxic patients (six FA and six OPCA) who did not receive any treatment. A 6-month trial at a double dose did not have any significant effect. This study indicates that phosphatidylcholine does not change the natural course of ataxias.

Ataxia↗
PubMed1987

Intralaminar distribution of neurotransmitter-related enzymes in cerebral cortex of Alzheimer's disease.

The intralaminar distribution of choline acetyltransferase, galactocerebrosides, gangliosides and proteins were determined in frontal (Brodmann's area 9) and temporal (Brodmann's area 22) cortices from subjects with autopsy-proven Alzheimer's disease and controls matched for sex, age and postmortem delay. In normal brain choline acetyltransferase (CAT) activity was higher in the II and IV layers in the temporal cortex, while in frontal cortex CAT activity was relatively high in the II-III layer, appearing as a single peak. The intracortical distribution of galactocerebrosides normally shows a trend to a higher activity from the pial surface to white matter either in frontal or temporal cortices. Higher concentrations of gangliosides were associated with the cell body layers in either frontal or temporal cortices. In either frontal and temporal cortices from 5 patients with Alzheimer's disease the pattern of intralaminar distribution of CAT activity was completely disrupted and it was significantly lower than in all cortical layers of the controls. Galactocerebrosides concentration was significantly decreased in the lower layers (IV, V and VI) in both frontal and temporal cortices and ganglioside sialic acid concentration was also decreased in the Alzheimer brain consistently in the lower (III-IV) layers of the frontal and temporal cortices. These observations indicate a widespread involvement of cholinergic activities through all cortical layers. However, the selective decrease in galactocerebroside concentration in the lower layers (IV-VI) suggests a selective loss of ascending fibers from subcortical nuclei. The decreased concentration of ganglioside sialic acid in lower layers suggests a selective axodendritic degeneration in these laminae of frontal association and temporal cortex in Alzheimer's disease.

Aged↗
PubMed1986

Abnormal platelet glutamate dehydrogenase activity and activation in dominant and nondominant olivopontocerebellar atrophy.

Glutamate dehydrogenase (GDH) activity and its allosteric modulation by purine nucleotides were studied in platelet preparations from 4 patients with a nondominant form of adult-onset olivopontocerebellar atrophy (OPCA) and in affected and nonaffected members of two families with a dominant form of OPCA. A partial deficiency of GDH activity (40 to 50% of control values) was present in 3 patients with nondominant OPCA and in 2 patients, father and son, with a dominant form of OPCA. Platelet GDH from these patients and controls was regularly inactivated by 2 mM guanosine-5'-triphosphate (GTP) and simulated one- to twofold by 2 mM adenosine-5'-diphosphate (ADP). In the presence of 0.2% Triton X-100, the activating effect of ADP was enhanced four- to sixfold. The partial deficiency in maximum catalytic activity observed in these patients persisted under all conditions used for enzyme assay. In affected members, but not in one unaffected member of another family with a dominant type of OPCA, GDH activity was in the control range but was not activated by ADP in either the presence or absence of Triton. These results suggest that there may be at least two possible alterations of GDH in patients with OPCA: one which decreases the maximum catalytic activity and one which impairs the regulatory properties of the enzyme. Furthermore, this study suggests that platelet GDH determination in patients with OPCA may provide a simple and useful tool to classify these disorders and to understand the basic pathophysiological mechanisms involved.

Adolescent↗
PubMed1986

Energy metabolism in demented brain.

The term dementia refers to a number of very complicated disorders of the brain with several morphological, biochemical and functional alterations. Several alterations occur in Alzheimer's disease. They include alteration in neurotransmitters related substances and changes in brain metabolic rate. Changes in metabolic activity are among the earliest and best documented of all modification reported in Alzheimer's brain. They appear to be correlate with the severity of the disease, and to be more marked in specific areas of the brain which appear to be clinically more involved. In this report will be discussed the observations on changes of cerebral glucose metabolic rate, cerebral oxygen consumption, cerebral blood flow reported in vivo in demented patients. The observations of changes in energy metabolism related enzymes and the relationship between these changes and those in neurotransmitters related substances will be also reviewed.

Alzheimer Disease↗
PubMed1983

Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain.

The activity of the pyruvate dehydrogenase complex (PDHC) was reduced in affected areas of brain from patients with Huntington disease (caudate, putamen) and Alzheimer disease (frontal cortex) where choline acetyltransferase (CAT) activity was low. PDHC was also deficient in an area (Huntington hippocampus) where CAT was not significantly reduced. The activity of fumarase, an inner mitochondrial marker, was normal in all areas examined. The activities of PDHC and CAT correlated well in caudate, putamen, and amygdala but not in hippocampus or frontal cortex. Both total activity and activation of PDHC were below normal in fibroblasts from 4 patients with C-21 trisomy Down syndrome, who are at very high risk to develop Alzheimer disease. However, no abnormality of PDHC was detected in Huntington or Alzheimer fibroblasts. Deficiency of PDHC may play a role in the pathophysiology of Huntington and Alzheimer diseases, although it does not appear to be a primary defect. Loss of tissue oxidative capacity may relate to the reduction in cerebral metabolic rate and blood flow which are characteristic of many dementing illnesses.

Alzheimer Disease↗