1. |
- Lord, Anna, 1979-, et al.
(author)
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Amyloid-β protofibril levels correlate with spatial learning in Arctic Alzheimer’s disease transgenic mice
- 2009
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In: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 276:4, s. 995-1006
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Journal article (peer-reviewed)abstract
- Oligomeric assemblies of amyloid-β (Aβ) are suggested to be central in the pathogenesis of Alzheimer's disease because levels of soluble Aβ correlate much better with the extent of cognitive dysfunctions than do senile plaque counts. Moreover, such Aβ species have been shown to be neurotoxic, to interfere with learned behavior and to inhibit the maintenance of hippocampal long-term potentiation. The tg-ArcSwe model (i.e. transgenic mice with the Arctic and Swedish Alzheimer mutations) expresses elevated levels of Aβ protofibrils in the brain, making tg-ArcSwe a highly suitable model for investigating the pathogenic role of these Aβ assemblies. In the present study, we estimated Aβ protofibril levels in the brain and cerebrospinal fluid of tg-ArcSwe mice, and also assessed their role with respect to cognitive functions. Protofibril levels, specifically measured with a sandwich ELISA, were found to be elevated in young tg-ArcSwe mice compared to several transgenic models lacking the Arctic mutation. In aged tg-ArcSwe mice with considerable plaque deposition, Aβ protofibrils were approximately 50% higher than in younger mice, whereas levels of total Aβ were exponentially increased. Young tg-ArcSwe mice showed deficits in spatial learning, and individual performances in the Morris water maze were correlated inversely with levels of Aβ protofibrils, but not with total Aβ levels. We conclude that Aβ protofibrils accumulate in an age-dependent manner in tg-ArcSwe mice, although to a far lesser extent than total Aβ. Our findings suggest that increased levels of Aβ protofibrils could result in spatial learning impairment.
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3. |
- Carlsson, Lars, et al.
(author)
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Early multidisciplinary assessment was associated with longer periods of sick leave : A randomized controlled trial in a primary health care centre
- 2013
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In: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 31:3, s. 141-146
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Journal article (peer-reviewed)abstract
- ObjectiveTo study the effects on sick leave from an early multidisciplinary assessment at a primary health care centre. Design. Randomized controlled trial.SettingPatients who saw GPs at a primary health care centre in mid-Sweden and asked for a sickness certificate for psychiatric or musculoskeletal diagnoses were invited to participate. Patients included were sick-listed for less than four weeks; 33 patients were randomized either to an assessment within a week by a physiotherapist, a psychotherapist, and an occupational therapist or to "standard care". The therapists used methods and tools they normally use in their clinical work.Main outcome measureProportion of patients still sick-listed three months after randomization, total and net days on sick leave, and proportion who were on part-time sick leave.ResultsAt follow-up after three months, in contrast to the pre-trial hypothesis, there was a trend toward a higher proportion of patients still sick-listed in the intervention group (7/18) as compared with the control group (3/15). The intervention group also had significantly longer sick-listing periods (mean 58 days) than the control group (mean 36 days) (p = 0.038). The proportion of patients who were part time sick-listed was significantly higher in the intervention group (10/18) than in the control group (2/15) (p = 0.027).ConclusionsIn this study an early multidisciplinary assessment was associated with longer periods on sick leave and more individuals on part-time sick leave.
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4. |
- Englund, Hillevi, 1980-, et al.
(author)
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Sensitive ELISA detection of amyloid-β protofibrils in biological samples
- 2007
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In: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 103:1, s. 334-345
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Journal article (peer-reviewed)abstract
- Amyloid-β (Aβ) protofibrils are known intermediates of the in vitro Aβ aggregation process and the protofibrillogenic Arctic mutation (APPE693G) provides clinical support for a pathogenic role of Aβ protofibrils in Alzheimer's disease (AD). To verify their in vivo relevance and to establish a quantitative Aβ protofibril immunoassay, Aβ conformation dependent monoclonal antibodies were generated. One of these antibodies, mAb158 (IgG2a), was used in a sandwich ELISA to specifically detect picomolar concentrations of Aβ protofibrils without interference from Aβ monomers or the amyloid precursor protein (APP). The specificity and biological significance of this ELISA was demonstrated using cell cultures and transgenic mouse models expressing human APP containing the Swedish mutation (APPKN670/671ML), or the Swedish and Arctic mutation in combination. The mAb158 sandwich ELISA analysis revealed presence of Aβ protofibrils in both cell and animal models, proving that Aβ protofibrils are formed not only in vitro, but also in vivo. Furthermore, elevated Aβ protofibril levels in the Arctic-Swedish samples emphasize the usefulness of the Arctic mutation as a model of enhanced protofibril formation. This assay provides a novel tool for investigating the role of Aβ protofibrils in AD and has the potential of becoming an important diagnostic assay.
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5. |
- Englund, Hillevi, 1980-
(author)
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Soluble amyloid-β aggregates in Alzheimer’s disease
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Soluble oligomeric aggregates of the amyloid-β (Aβ) peptide are suggested to initiate Alzheimer's disease (AD), leading to impaired synapse signalling, widespread neuronal death and loss of cognitive functions. These aggregates seem tightly linked to disease progression, and have therefore gained much attention as potential novel disease markers. In this thesis soluble oligomeric Aβ aggregates in general, and the Aβ protofibril species in particular, have been investigated with the aim to quantify and determine their role in AD pathogenesis. Sandwich-ELISAs specifically measuring Aβ42 peptides are widely used both in AD research and as complements for clinical diagnosis. Here it was demonstrated that presence of soluble Aβ aggregates disturbs such analyses, making it difficult to interpret the results. This discovery was made through analyses of samples from cell- and mouse models carrying the AD causing 'Arctic' APP mutation. When analyzed by ELISA, Aβ42 levels were reduced in Arctic samples, in contrast to levels measured by denaturing SDS-PAGE Western blot. The same divergence in Aβ42-levels between analyses was observed in CSF samples from Down syndrome infants. The discrepancy between methods was hypothesized to be due to presence of soluble Aβ aggregates leading to impaired ELISA detection caused by epitope masking. This was confirmed by developing a protofibril specific ELISA, by which samples from Arctic cell- and mouse models were demonstrated to have enhanced Aβ protofibril levels. AD patients have reduced ELISA-measured Aβ42-levels in CSF compared to healthy controls. To test if this reduction was due to oligomeric Aβ species present in AD CSF, Aβ42-levels were analyzed under both denaturing and non-denaturing conditions. These two measures were combined and an Aβ42 oligomer ratio established. Higher ratios were found in AD patients than healthy controls, implying that Aβ oligomers are present in CSF during Alzheimer pathogenesis. The observations from AD patients and young Down syndrome individuals suggest that Aβ42 oligomer formation is an early mechanism of AD pathogenesis, which potentially could be used as a biomarker to monitor disease development.
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- Jonung, Lars, et al.
(author)
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Beslutsfattarnas syn på riksbankens politik
- 1993. - 1
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In: Från räntereglering till inflationsnorm. Det finansiella systemet och Riksbankens politik 1945-1990. - 9171504737 ; , s. 385-399
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Book chapter (other academic/artistic)
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- Jonung, Lars, et al.
(author)
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Kreditregleringarnas uppgång och fall
- 1993. - 1
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In: Från räntereglering till inflationsnorm. Det finansiella systemet och Riksbankens politik 1945-1990. - 9171504737 ; , s. 315-322
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Book chapter (other academic/artistic)
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9. |
- Jonung, Lars, et al.
(author)
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Riksbankens politik 1945-1990. En krönika
- 1993. - 1
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In: Från räntereglering till inflationsnorm : det finansiella systemet och Riksbankens politik 1945-1990. - 9171504737 ; , s. 288-298
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Book chapter (other academic/artistic)
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10. |
- Jonung, Lars, et al.
(author)
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Riksbankens politik 1945-1990. En syntes
- 1993
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In: rån räntereglering till inflationsnorm : det finansiella systemet och Riksbankens politik 1945-1990. - 9171504737 ; , s. 400-428
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Book chapter (other academic/artistic)
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