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Biomedical subjects

Jan Marcusson

Publications and source records attributed to Jan Marcusson.

15 recordsLinked to original sources
PubMed2006

Oxidative stress and Alzheimer disease: the autophagy connection?

Intraneuronal accumulation of amyloid beta-protein (Abeta) is believed to be responsible for degeneration and apoptosis of neurons and consequent senile plaque formation in Alzheimer disease (AD), the main cause of senile dementia. Oxidative stress, an early determinant of AD, has been recently found to induce intralysosomal Abeta accumulation in cultured differentiated neuroblastoma cells through activation of macroautophagy. Because Abeta is known to destabilize lysosomal membranes, potentially resulting in apoptotic cell death, this finding suggests the involvement of oxidative stress-induced macroautophagy in the pathogenesis of AD.

Alzheimer Disease↗
PubMed2006

Oxidative stress induces intralysosomal accumulation of Alzheimer amyloid beta-protein in cultured neuroblastoma cells.

Oxidative stress is considered important for the pathogenesis of Alzheimer's disease (AD), which is characterized by the formation of extracellular senile plaques, mainly composed of amyloid beta-protein (Abeta). Abeta also accumulates within AD neurons and is believed to exert cellular toxicity through lysosomal labilization. We report that the exposure of human neuroblastoma cells to hyperoxia (40% vs. 8% ambient oxygen) induced the accumulation of large (over 1 microM) Abeta-containing lysosomes, which were not typical of control cells, showing a distinct localization of Abeta and lysosomal markers. An inhibitor of autophagy, 3-methyladenine, suppressed the effect of hyperoxia. The results suggest a link between the involvement of oxidative stress and lysosomes in AD.

Alzheimer Disease↗
PubMed2005

Autophagy of amyloid beta-protein in differentiated neuroblastoma cells exposed to oxidative stress.

Oxidative stress is considered important for the pathogenesis of Alzheimer disease (AD), which is characterized by the formation of senile plaques rich in amyloid beta-protein (Abeta). Abeta cytotoxicity has been found dependent on lysosomes, which are abundant in AD neurons and are shown to partially co-localize with Abeta. To determine whether oxidative stress has any influence on the relationship between lysosomes and Abeta1-42 (the most toxic form of Abeta), we studied the effect of hyperoxia (40% versus 8% ambient oxygen) on the intracellular localization of Abeta1-42 (assessed by immunocytochemistry) in retinoic acid differentiated SH-SY5Y neuroblastoma cells maintained in serum-free OptiMEM medium. In control cells, Abeta1-42 was mainly localized to small non-lysosomal cytoplasmic granules. Only occasionally Abeta1-42 was found in large (over 1 microm) lysosomal-associated membrane protein 2 positive vacuoles, devoid of the early endosomal marker rab5. These large Abeta1-42 -containing lysosomes were not detectable in the presence of serum (known to suppress autophagy), while their number increased dramatically (up to 24-fold) after exposure of cells to hyperoxia during 5 days. Activation of autophagy by hyperoxia was confirmed by transmission electron microscopy. Furthermore, an inhibitor of autophagic sequestration 3-methyladenine prevented the accumulation of Abeta1-42 -positive lysosomes due to hyperoxia. In parallel experiments, intralysosomal accumulation of Abeta1-40 following oxidative stress has been found as well. The results suggest that Abeta can be autophagocytosed and its accumulation within neuronal lysosomes is enhanced by oxidative stress.

Amyloid beta-Peptides↗
PubMed2005

Evaluation of factors of importance for clinical dementia diagnosis.

Diagnosing clinical dementia is based on an assessment of different variables, such as the patient's medical history, known risk factors, and biochemical features. Partial least squares discriminant analysis was used to evaluate variables of importance for diagnosing dementia in a clinical dementia population. Polymorphism for genotypes of glutathione S-transferase (GST) and sulfotransferase 1A1, hypothetically of importance in dementia disorders, was also included in the analysis. The study population consisted of 73 patients with Alzheimer's disease (AD), 14 with mixed dementia, 75 patients with vascular dementia, and 28 control cases. We found that several of the variables, such as the presence of ApoE4 allele, high cerebrospinal fluid levels of total tau protein, low levels of beta-amyloid((1-42)), and a low score on the Mini-Mental State Examination, facilitated a discrimination between the diagnoses compared with the controls. The different diagnoses overlapped. There were indications that genotypes of GSTs contributed to a subgrouping within AD.

Aged↗
PubMed2004

Rivastigmine as a modulator of the neuronal glutamate transporter rEAAC1 mRNA expression.

Alzheimer's disease is a neurodegenerative disorder that affects the cholinergic, glutamatergic and monoaminergic systems in the neocortex and hippocampus. Today, the major pharmacological treatment involves the use of acetylcholinesterase inhibitors (AChEIs). In this study, an in situ hybridisation technique (using digoxigenin-labelled cRNA probes) was used to elucidate changes in mRNA expression of the neuronal glutamate transporter, rat excitatory amino carrier 1 (rEAAC1), after treatment with the AChEI rivastigmine. Compared with saline-treated rats, the rats subchronically (3 days) and chronically (21 days), but not acutely, treated with rivastigmine showed a significant increase in rEAAC1 mRNA expression in the hippocampal areas cornu anterior 1 (CA1), CA2, CA3 and dentate gyrus (p < 0.01), but not in the cortical areas. These results provide the first evidence that the glutamatergic system is modulated following acetylcholinesterase inhibition by rivastigmine, a finding, which is likely to be of importance for the clinical effects.

Administration, Oral↗
PubMed2004

Modulation of neuronal glutamate transporter rEAAC1 mRNA expression in rat brain by amitriptyline.

Glutamate transporters regulate the glutamate concentration in the synaptic cleft within the CNS, a regulation required for normal brain function. In several neurological conditions, the amount of glutamate is altered. One reason for the changes in glutamate concentration might be impaired glutamate transporter function. In this study, an in situ hybridisation technique has been used to elucidate changes in mRNA expression of the glutamate transporter, excitatory amino acid carrier 1 (EAAC1), after treatment with the tricyclic antidepressant (TCA) amitriptyline. The results lead to the suggestion that treatment with tricyclic antidepressants leads to changes in the EAAC1 mRNA expression in rat brain suggesting involvement of the glutamate system in the tricyclic treatment of depression.

Amino Acid Transport System X-AG↗
PubMed2004

CT brain findings in clinical dementia investigation--underestimation of mixed dementia.

Dementia has been found to display a more heterogeneous clinical picture than previously recognized. We investigated brain changes on computed tomography (CT) in a clinical dementia population consisting of 67 cases with Alzheimer's disease (AD), 13 with mixed dementia (AD and vascular dementia, VaD), 71 with VaD, and 12 cases that were not demented. Temporal cortical atrophy and atrophy around the temporal horns were more common in patients with mixed dementia compared to patients with VaD and the non-demented, respectively. Frontal white matter changes were present in 64% of AD, in 85% of mixed dementia and in 79% of VaD cases, but there were no differences between the dementia groups. Lacunes were present in almost 40% of AD cases and in 80 and 85% of VaD and mixed dementia cases, respectively. Only 14% of the VaD cases had large infarcts on the CT. We conclude that large infarcts were rare, even in VaD cases. The increased incidence of white matter changes and lacunes in AD patients strongly indicates an underestimation of the mixed dementia diagnosis. More distinct criteria for this diagnostic category are warranted.

Aged↗
PubMed2003

The Canadian Occupational Performance Measure as an outcome measure and team tool in a day treatment programme.

PURPOSE: To investigate the usefulness of the Canadian Occupational Performance Measure (COPM) in a day treatment programme for clients with rheumatoid arthritis. METHOD: The study was conducted in two parts. In the first part rehabilitation without changes in the programme was performed (n = 16). After that the COPM was introduced to all team members. In part two the COPM was used (n = 40). Clients' experiences of participation in the process were studied via a structured interview 2 - 4 weeks after discharge in both parts. Qualitative interviews were conducted with team members before part one and after completion of part two. RESULTS: Staff expressed that the COPM improved client participation in the rehabilitation process. Goals were formulated distinctly, and focused on activity and performance rather than function. Team conferences were focused on the client's needs. Outcome was considered clear and evident to the client. The changes in client routines demands thorough introduction, support and involvement, and takes time. Involvement and motivation for changing practice were difficult to obtain, this could be a result of a large staff turnover during the data collection period. CONCLUSIONS: The COPM should be seen as an aid to ensuring client participation in the goal formulation process, and facilitating treatment planning and evaluation of outcome.

Arthritis, Rheumatoid↗
PubMed2002

Improved client participation in the rehabilitation process using a client-centred goal formulation structure.

The aim was to evaluate whether the use of a client-centred instrument, the Canadian Occupational Performance Measure (COPM), affects the patients' perception of active participation in the rehabilitation process. The study included 155 patients in the experiment group and 55 in the control group, within geriatric, stroke, and home rehabilitation. The COPM was used in the experiment group. A structured interview was performed within 2-4 weeks after discharge with 88 patients in the experiment group and 30 patients in the control group. The results show significant differences between the groups. More patients in the experiment group perceived that treatment goals were identified, were able to recall the goals, felt that they were active participants in the goal formulation process, and perceived themselves better able to manage after completed rehabilitation compared with patients in the control group. The study indicates that the COPM improves client participation in the rehabilitation process.

Activities of Daily Living↗
PubMed2002

Increased [(3)H]tiagabine binding to GAT-1 in the cingulate cortex in schizophrenia.

Postmortem samples from individuals with schizophrenia (n = 13) and control subjects (n = 10) were investigated for binding of [(3)H]tiagabine to GABA transporter-1 GAT-1. The binding was analyzed in the cingulate cortex and the caudate nucleus. There were no differences in binding affinity between the groups in any of the investigated areas. The maximum number of binding sites (B(max)) was elevated in the schizophrenic cingulate cortex compared to controls (1,264 +/- 96 vs. 860 +/- 123 fmol/mg of protein). The B(max) in the caudate nucleus for schizophrenics (426 +/- 40 fmol/mg of protein) was the same as for controls (495 +/- 69 fmol/mg of protein). The increase in GAT-1 in schizophrenia could be explained by a modulatory upregulation in the cingulate cortex.

Aged↗
PubMed2002

Caudate nucleus dopamine d(2) receptors in vascular dementia.

Caudate nucleus dopamine (DA) D(2) receptors were studied in patients with vascular dementia (VaD) and in a control group using [(3)H]raclopride as a radioligand. There was no significant difference in the number of DA D(2) receptors in the VaD group as compared with controls. The binding affinity was significantly lower in the VaD group. When the VaD group was subdivided into subjects with or without neuroleptic treatment, there were no differences in the numbers of receptors as compared with controls, and the significant differences in binding affinity remained for both VaD subgroups. The present results are discussed with reference to the previous finding of a reduced density of caudate nucleus DA uptake sites in the same VaD group and to results from studies on DA D(2) receptors in Alzheimer's disease and Parkinson's disease.

Aged↗
PubMed2002

Cerebrospinal fluid phospho-tau, total tau and beta-amyloid(1-42) in the differentiation between Alzheimer's disease and vascular dementia.

The two most frequently examined biomarkers in the diagnosis of dementia are cerebrospinal fluid (CSF) tau and beta-amyloid(1-42) (Abeta(1-42)). An assay for tau phosphorylated at threonine 181 (phospho-tau) has recently been developed. We studied these three markers in patients with possible Alzheimer's disease (AD; n = 23), probable AD (n = 50), AD with relevant cerebrovascular disease (AD with CVD; n = 14), possible vascular dementia (VaD; n = 39), probable VaD (n = 36), cognitively impaired (n = 13) and 27 neurologically healthy controls. Compared with the controls, tau levels were significantly increased in possible AD, probable AD, AD with CVD and probable VaD. Abeta(1-42) was decreased in all dementia groups compared with the controls. In contrast, phospho-tau levels were increased only in probable AD compared with the controls. From the results of the present study, it is concluded that neither measurement of phospho-tau, tau nor Abeta(1-42) in CSF can discriminate entirely between dementia and cognitively non-disturbed controls or between dementia of different aetiologies in the clinical diagnostic procedure.

Aged↗
PubMed2002

Clinical utility of the Canadian Occupational Performance Measure--Swedish version.

The Canadian Occupational Performance Measure (COPM) is an individualised outcome measure intended to detect change in a client's perception of occupational performance over time. The aim of this study was to test the clinical utility of the Swedish version of the COPM. Data was collected from 27 occupational therapists in six focus groups. Emerging themes included goal-setting, preparations, limitations, interactions with clients, and impact on practice. The results indicated that the COPM is helpful in the goal-setting process and in planning treatment interventions. Therapists need knowledge about the theoretical foundation of the instrument and a personal interview technique. Problems were found using the instrument with clients who had poor insight or in acute settings. The COPM facilitated feedback on improvement over time. In summary, the COPM ensures a client-centred approach, facilitates communication within the rehabilitation team, and encourages therapists in their professional role.

Adult↗
PubMedDate not supplied

Galantamine demonstrates efficacy and safety in elderly patients with Alzheimer disease.

Alzheimer disease (AD) treatment guidelines state that cholinergic agents are not cost-effective in patients with more severe disease. Because many physicians may deem an older patient unlikely to respond to treatment, older AD patients may remain untreated. Galantamine (Reminyl), a novel cholinergic agent, is effective in mild to moderate AD. This post hoc analysis of pooled phase III galantamine clinical trials was designed to assess whether older (> or =80 years) and younger (< or =79 years) AD patients experience similar benefits with galantamine based on changes in the ADAS-cog and CIBIC-plus. Mean ADAS-cog scores for older patients treated with galantamine 24 mg/day significantly improved versus baseline and versus placebo at month 3. Cognitive improvement was maintained versus placebo at month 6; the ADAS-cog score for placebo patients dropped below baseline at month 6. Change in CIBIC-plus for galantamine was significantly different from placebo at months 5 to 6. Mean ADAS-cog score in older patients taking galantamine for 12 months remained above baseline. The score for patients taking placebo for 6 months before switching to galantamine did not differ significantly from baseline at 12 months but was lower than in patients receiving galantamine for 12 months. Incidence of adverse events in patients > 80 years was similar to that in the overall study population. Galantamine maintained cognitive and global function in patients > 80 years with mild to moderate AD for at least 5 to 6 months and cognitive efficacy for 12 months. Prescribing approved therapies such as galantamine for older patients with AD is recommended.

Age Factors↗