uu.seUppsala University Publications
Change search
Refine search result
1 - 10 of 10
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Adamczuk, Katarzyna
    et al.
    Katholieke Univ Leuven, Lab Cognit Neurol, B-3000 Louvain, Belgium.;Katholieke Univ Leuven, Leuven Inst Neurosci & Dis, Alzheimer Res Ctr, B-3000 Louvain, Belgium..
    Schaeverbeke, Jolien
    Katholieke Univ Leuven, Lab Cognit Neurol, B-3000 Louvain, Belgium.;Katholieke Univ Leuven, Leuven Inst Neurosci & Dis, Alzheimer Res Ctr, B-3000 Louvain, Belgium..
    Vanderstichele, Hugo M. J.
    ADx NeuroSci, B-9052 Ghent, Belgium..
    Lilja, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. GE Healthcare, S-75125 Uppsala, Sweden..
    Nelissen, Natalie
    Katholieke Univ Leuven, Lab Cognit Neurol, B-3000 Louvain, Belgium.;Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England..
    Van Laere, Koen
    Katholieke Univ Leuven, Leuven Inst Neurosci & Dis, Alzheimer Res Ctr, B-3000 Louvain, Belgium.;Katholieke Univ Leuven, Nucl Med & Mol Imaging Dept, B-3000 Louvain, Belgium.;Katholieke Univ Leuven Hosp, B-3000 Louvain, Belgium..
    Dupont, Patrick
    Katholieke Univ Leuven, Lab Cognit Neurol, B-3000 Louvain, Belgium.;Katholieke Univ Leuven, Leuven Inst Neurosci & Dis, Alzheimer Res Ctr, B-3000 Louvain, Belgium..
    Hilven, Kelly
    Katholieke Univ Leuven, Lab Neuroimmunol, B-3000 Louvain, Belgium..
    Poesen, Koen
    Katholieke Univ Leuven, Lab Mol Neurobiomarker Res, B-3000 Louvain, Belgium.;UZ Leuven, Lab Med, B-3000 Louvain, Belgium..
    Vandenberghe, Rik
    Katholieke Univ Leuven, Lab Cognit Neurol, B-3000 Louvain, Belgium.;Katholieke Univ Leuven, Leuven Inst Neurosci & Dis, Alzheimer Res Ctr, B-3000 Louvain, Belgium.;Univ Hosp Leuven, Dept Neurol, B-3000 Louvain, Belgium..
    Diagnostic value of cerebrospinal fluid A beta ratios in preclinical Alzheimer's disease2015In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 7, article id 75Article in journal (Refereed)
    Abstract [en]

    Introduction: In this study of preclinical Alzheimer's disease (AD) we assessed the added diagnostic value of using cerebrospinal fluid (CSF) A beta ratios rather than A beta 42 in isolation for detecting individuals who are positive on amyloid positron emission tomography (PET). Methods: Thirty-eight community-recruited cognitively intact older adults (mean age 73, range 65-80 years) underwent F-18-flutemetamol PET and CSF measurement of A beta 1-42, A beta 1-40, A beta 1-38, and total tau (ttau). F-18-flutemetamol retention was quantified using standardized uptake value ratios in a composite cortical region (SUVRcomp) with reference to cerebellar grey matter. Based on a prior autopsy validation study, the SUVRcomp cut-off was 1.57. Sensitivities, specificities and cut-offs were defined based on receiver operating characteristic analysis with CSF analytes as variables of interest and F-18-flutemetamol positivity as the classifier. We also determined sensitivities and CSF cut-off values at fixed specificities of 90 % and 95 %. Results: Seven out of 38 subjects (18 %) were positive on amyloid PET. A beta 42/ttau, A beta 42/A beta 40, A beta 42/A beta 38, and A beta 42 had the highest accuracy to identify amyloid-positive subjects (area under the curve (AUC) >= 0.908). A beta 40 and A beta 38 had significantly lower discriminative power (AUC = 0.571). When specificity was fixed at 90 % and 95 %, A beta 42/ttau had the highest sensitivity among the different CSF markers (85.71 % and 71.43 %, respectively). Sensitivity of A beta 42 alone was significantly lower under these conditions (57.14 % and 42.86 %, respectively). Conclusion: For the CSF-based definition of preclinical AD, if a high specificity is required, our data support the use of A beta 42/ttau rather than using A beta 42 in isolation.

  • 2.
    Eyjolfsdottir, Helga
    et al.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Geriatr, S-17176 Stockholm, Sweden..
    Eriksdotter, Maria
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Geriatr, S-17176 Stockholm, Sweden..
    Linderoth, Bengt
    Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Neurosurg, Bldg R3 02, S-17176 Stockholm, Sweden..
    Lind, Goran
    Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Neurosurg, Bldg R3 02, S-17176 Stockholm, Sweden..
    Juliusson, Bengt
    NsGene Inc, 225 Chapman St, Providence, RI 02905 USA..
    Kusk, Philip
    NsGene Inc, 225 Chapman St, Providence, RI 02905 USA..
    Almkvist, Ove
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden..
    Andreasen, Niels
    Karolinska Univ Hosp, Dept Geriatr, S-17176 Stockholm, Sweden..
    Blennow, Kaj
    Univ Gothenburg, Dept Clin Neurosci, Clin Neurochem Lab, S-41345 Gothenburg, Sweden..
    Ferreira, Daniel
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden..
    Westman, Eric
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden..
    Nennesmo, Inger
    Karolinska Univ Hosp, Dept Lab Med, Sect Pathol, S-17176 Stockholm, Sweden..
    Karami, Azadeh
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden..
    Darreh-Shori, Taher
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden..
    Kadir, Ahmadul
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden..
    Nordberg, Agneta
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Geriatr, S-17176 Stockholm, Sweden..
    Sundström, Erik
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;Stiftelsen Stockholms Sjukhem, Mariebergsgatan 22, S-11235 Stockholm, Sweden..
    Wahlund, Lars-Olof
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Geriatr, S-17176 Stockholm, Sweden..
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wiberg, Maria
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Med Imaging & Technol, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Radiol, S-17176 Stockholm, Sweden..
    Winblad, Bengt
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Geriatr, S-17176 Stockholm, Sweden..
    Seiger, Ake
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;Stiftelsen Stockholms Sjukhem, Mariebergsgatan 22, S-11235 Stockholm, Sweden..
    Wahlberg, Lars
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, S-17177 Stockholm, Sweden.;NsGene Inc, 225 Chapman St, Providence, RI 02905 USA..
    Almqvist, Per
    Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Neurosurg, Bldg R3 02, S-17176 Stockholm, Sweden..
    Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer's disease patients: application of a second-generation encapsulated cell biodelivery device2016In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 8, article id 30Article in journal (Refereed)
    Abstract [en]

    Background: Targeted delivery of nerve growth factor (NGF) has emerged as a potential therapy for Alzheimer's disease (AD) due to its regenerative effects on basal forebrain cholinergic neurons. This hypothesis has been tested in patients with AD using encapsulated cell biodelivery of NGF (NGF-ECB) in a first-in-human study. We report our results from a third-dose cohort of patients receiving second-generation NGF-ECB implants with improved NGF secretion. Methods: Four patients with mild to moderate AD were recruited to participate in an open-label, phase Ib dose escalation study with a 6-month duration. Each patient underwent stereotactic implant surgery with four NGF-ECB implants targeted at the cholinergic basal forebrain. The NGF secretion of the second-generation implants was improved by using the Sleeping Beauty transposon gene expression technology and an improved three-dimensional internal scaffolding, resulting in production of about 10 ng NGF/device/day. Results: All patients underwent successful implant procedures without complications, and all patients completed the study, including implant removal after 6 months. Upon removal, 13 of 16 implants released NGF, 8 implants released NGF at the same rate or higher than before the implant procedure, and 3 implants failed to release detectable amounts of NGF. Of 16 adverse events, none was NGF-, or implant-related. Changes from baseline values of cholinergic markers in cerebrospinal fluid (CSF) correlated with cortical nicotinic receptor expression and Mini Mental State Examination score. Levels of neurofilament light chain (NFL) protein increased in CSF after NGF-ECB implant, while glial fibrillary acidic protein (GFAP) remained stable. Conclusions: The data derived from this patient cohort demonstrate the safety and tolerability of sustained NGF release by a second-generation NGF-ECB implant to the basal forebrain, with uneventful surgical implant and removal of NGF-ECB implants in a new dosing cohort of four patients with AD.

  • 3.
    Gunnarsson, Malin Degerman
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Blennow, Kaj
    Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Neurosci & Physiol, Clin Neurochem Lab, SE-43180 Molndal, Sweden..
    Basun, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    High tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer's disease2016In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 8, article id 22Article in journal (Refereed)
    Abstract [en]

    Background: Increased concentrations of cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau, as well as decreased amyloid-beta 42 peptide, are biomarkers of Alzheimer's disease (AD) pathology, but few studies have shown an association with AD progression rate. We hypothesized that high CSF tau, as a marker of ongoing neurodegeneration, would predict a more aggressive course of AD, using time to nursing home placement (NHP) as the main outcome. Methods: Our sample inlcuded 234 patients with mild cognitive impairment (MCI) due to AD (n = 134) or mild to moderate AD (n = 100) who underwent lumbar puncture at a memory clinic and were followed for 2-11 years (median 4.9 years). Results: Individuals with CSF t-tau in the highest quartile (>= 900 ng/L) had a higher ratio of NHP, both in the total cohort and in patients with MCI only (adjusted HR 2.17 [95 % CI 1.24-3.80]; HR 2.37 [95 % CI 1.10-5.09], respectively), than the lowest quartile. The association between high t-tau levels and future steep deterioration was confirmed in analyses with conversion to moderate dementia (HR 1.66; 95 % CI 1.08-2.56), rapid decline in Mini Mental State Examination score (>= 4-point drop/12 months), and dying in severe dementia as outcomes. Conclusions: To our knowledge, this is the first study to show that high CSF t-tau levels predict early NHP and conversion to moderate dementia in an AD cohort. Selecting patients with high CSF t-tau, indicating more aggressive neurodegeneration and steeper decline, for AD immunotherapy trials might increase the possibility of showing contrast between active treatment and placebo.

  • 4.
    Hansson, Oskar
    et al.
    Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Malmo, Sweden;Skane Univ Hosp, Memory Clin, Malmo, Sweden.
    Svensson, Martina
    Lund Univ, Dept Expt Med Sci, Expt Neuroinflammat Lab, S-22184 Lund, Sweden.
    Gustaysson, Anna-Marta
    Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Malmo, Sweden;Skane Univ Hosp, Memory Clin, Malmo, Sweden.
    Andersson, Emelie
    Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Malmo, Sweden.
    Yang, Yiyi
    Lund Univ, Dept Expt Med Sci, Expt Neuroinflammat Lab, S-22184 Lund, Sweden.
    Nagga, Katarina
    Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Malmo, Sweden;Linkoping Univ, Dept Acute Internal Med & Geriatr, Linkoping, Sweden.
    Hållmarker, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Deierborg, Tomas
    Lund Univ, Dept Expt Med Sci, Expt Neuroinflammat Lab, S-22184 Lund, Sweden.
    Midlife physical activity is associated with lower incidence of vascular dementia but not Alzheimer's disease2019In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 11, article id 87Article in journal (Refereed)
    Abstract [en]

    Background: Physical activity might reduce the risk of developing dementia. However, it is still unclear whether the protective effect differs depending on the subtype of dementia. We aimed to investigate if midlife physical activity affects the development of vascular dementia (VaD) and Alzheimer's disease (AD) differently in two large study populations with different designs.

    Methods: Using a prospective observational design, we studied whether long-distance skiers of the Swedish Vasaloppet (n = 197,685) exhibited reduced incidence of VaD or AD compared to matched individuals from the general population (n = 197,684) during 21 years of follow-up (median 10, interquartile range (IQR) 5-15 years). Next, we studied the association between self-reported physical activity, stated twice 5 years apart, and incident VaD and AD in 20,639 participants in the Swedish population-based Malmo Diet and Cancer Study during 18 years of follow-up (median 15, IQR 14-17 years). Finally, we used a mouse model of AD and studied brain levels of amyloid-beta, synaptic proteins, and cognitive function following 6 months of voluntary wheel running.

    Results Vasaloppet skiers (median age 36.0 years [IQR 29.0-46.0], 38% women) had lower incidence of all-cause dementia (adjusted hazard ratio (HR) 0.63, 95% CI 0.52-0.75) and VaD (adjusted HR 0.49, 95% CI 0.33-0.73), but not AD, compared to non-skiers. Further, faster skiers exhibited a reduced incidence of VaD (adjusted HR 0.38, 95% CI 0.16-0.95), but not AD or all-cause dementia compared to slower skiers. In the Malmo Diet and Cancer Study (median age 57.5 years [IQR 51.0-63.8], 60% women), higher physical activity was associated with reduced incidence of VaD (adjusted HR 0.65, 95% CI 0.49-0.87), but not AD nor all-cause dementia. These findings were also independent of APOE-epsilon 4 genotype. In AD mice, voluntary running did not improve memory, amyloid-beta, or synaptic proteins.

    Conclusions: Our results indicate that physical activity in midlife is associated with lower incidence of VaD. Using three different study designs, we found no significant association between physical activity and subsequent development of AD.

  • 5.
    Logovinsky, Veronika
    et al.
    Eisai Inc, 100 Tice Blvd, Woodcliff Lake, NJ 07677 USA..
    Satlin, Andrew
    Eisai Inc, 100 Tice Blvd, Woodcliff Lake, NJ 07677 USA..
    Lai, Robert
    Eisai Inc, 100 Tice Blvd, Woodcliff Lake, NJ 07677 USA..
    Swanson, Chad
    Eisai Inc, 100 Tice Blvd, Woodcliff Lake, NJ 07677 USA..
    Kaplow, June
    Eisai Inc, 100 Tice Blvd, Woodcliff Lake, NJ 07677 USA..
    Osswald, Gunilla
    BioArctic Neurosci AB, Warfvinges Vag 35, S-11251 Stockholm, Sweden..
    Basun, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. BioArctic Neurosci AB, Warfvinges Vag 35, S-11251 Stockholm, Sweden..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. BioArctic Neurosci AB, Warfvinges Vag 35, S-11251 Stockholm, Sweden..
    Safety and tolerability of BAN2401 - a clinical study in Alzheimer's disease with a protofibril selective A beta antibody2016In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 8, article id 14Article in journal (Refereed)
    Abstract [en]

    Background: Several monoclonal antibodies for the treatment of Alzheimer's disease (AD) have been in development over the last decade. BAN2401 is a monoclonal antibody that selectively binds soluble amyloid beta (A beta) protofibrils.

    Methods: Here we describe the first clinical study with BAN2401. Safety and tolerability were investigated in mild to moderate AD. A study design was used with staggered parallel single and multiple ascending doses, from 0.1 mg/kg as a single dose to 10 mg/kg biweekly for four months. The presence of amyloid related imaging abnormalities (ARIA, E for edema, H for hemorrhage) was assessed with magnetic resonance imaging (MRI). Cerebrospinal fluid (CSF) and plasma samples were analyzed to investigate pharmacokinetics (PK) and effects on biomarkers.

    Results: The incidence of ARIA-E/H on MRI was comparable to that of placebo. BAN2401 exposure was approximately dose proportional, with a serum terminal elimination half-life of similar to 7 days. Only a slight increase of plasma A beta((1-40)) was observed but there were no measurable effects of BAN2401 on CSF biomarkers. On the basis of these findings Phase 2b efficacy study has been initiated in early AD.

    Conclusions: BAN2401 was well-tolerated across all doses. The PK profile has guided us for selecting dose and dose regimens in the ongoing phase 2b study. There was no clear guidance for an effective dose based on biomarkers.

  • 6.
    Saint-Aubert, Laure
    et al.
    Karolinska Inst, Dept NVS, Ctr Alzheimer Res, Div Translat Alzheimer Neurobiol, Novum 5th Floor, S-14157 Huddinge, Sweden..
    Almkvist, Ove
    Karolinska Inst, Dept NVS, Ctr Alzheimer Res, Div Translat Alzheimer Neurobiol, Novum 5th Floor, S-14157 Huddinge, Sweden.;Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden.;Stockholm Univ, Dept Psychol, Stockholm, Sweden..
    Chiotis, Konstantinos
    Karolinska Inst, Dept NVS, Ctr Alzheimer Res, Div Translat Alzheimer Neurobiol, Novum 5th Floor, S-14157 Huddinge, Sweden..
    Almeida, Rita
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Univ Uppsala Hosp, PET Ctr, Uppsala, Sweden..
    Nordberg, Agneta
    Karolinska Inst, Dept NVS, Ctr Alzheimer Res, Div Translat Alzheimer Neurobiol, Novum 5th Floor, S-14157 Huddinge, Sweden.;Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden..
    Regional tau deposition measured by [F-18]THK5317 positron emission tomography is associated to cognition via glucose metabolism in Alzheimer's disease2016In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 8, article id 38Article in journal (Refereed)
    Abstract [en]

    Background: The recent development of tau-specific positron emission tomography (PET) tracers has allowed in vivo quantification of regional tau deposition and offers the opportunity to monitor the progression of tau pathology along with cognitive impairment. In this study, we investigated the relationships of cerebral tau deposition ([F-18]THK5317-PET) and metabolism ([F-18]FDG-PET) with concomitant cognitive function in patients with probable Alzheimer's disease (AD). Methods: Nine patients diagnosed with AD dementia and 11 with prodromal AD (mild cognitive impairment, amyloid-positive on [C-11]PiB-PET) were included in this study. All patients underwent PET scans using each tracer, as well as episodic memory and global cognition assessment. Linear models were used to investigate the association of regional [F-18]THK5317 retention and [F-18]FDG uptake with cognition. The possible mediating effect of local metabolism on the relationship between tau deposition and cognitive performance was investigated using mediation analyses. Results: Significant negative associations were found between [F-18]THK5317 regional retention, mainly in temporal regions, and both episodic memory and global cognition. Significant positive associations were found between [F-18]FDG regional uptake and cognition. The association of [F-18]FDG with global cognition was regionally more extensive than that of [F-18]THK5317, while the opposite was observed with episodic memory, suggesting that [F-18]THK5317 retention might be more sensitive than [F-18]FDG regional uptake to early cognitive impairment. Finally, [F-18]FDG uptake had a mediating effect on the relationship between [F-18]THK5317 retention in temporal regions and global cognition. Conclusions: These findings suggest a mediating role for local glucose metabolism in the observed association between in vivo tau deposition and concomitant cognitive impairment in AD.

  • 7.
    Syvänen, Stina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Hultqvist, Greta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Gustavsson, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gumucio, Astrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Laudon, Hanna
    BioArctic AB, Stockholm, Sweden.
    Söderberg, Linda
    BioArctic AB, Stockholm, Sweden.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. BioArctic AB, Stockholm, Sweden.
    Sehlin, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Efficient clearence of A beta protofibrils in A beta PP-transgenic mice treated with a brain-penetrating bifunctional antibody2018In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 10, article id 49Article in journal (Refereed)
    Abstract [en]

    Background: Amyloid-beta (A beta) immunotherapy is one of the most promising disease-modifying strategies for Alzheimer's disease (AD) Despite recent progress targeting aggregated forms of A beta, low antibody brain penetrance remains a challenge In the piesent study, we used transferrin receptor (TfR)-mediated transcytosis to facilitate brain uptake of our previously developed A beta protofibril-selective mAb158, with the aim of increasing the efficacy of immunotherapy directed toward soluble A beta protofibills. Methods: A beta protein precursor (A beta PP)-transgenic mice (tg-ArcSwe) were given a single dose of mAb158, modified for TfR-mediated transcytosis (RmAb158-scFvSDB), in companson with an equimolar dose or a tenfold higher dose of unmodified recombinant mAb158 (RmAb158) Soluble A beta protofibrills and total A beta in the brain were measured by enzyme-linked immunosorbent assay (ELISA) Brain distribution of radiolabeled antibodies was visualized by positron emission tomography (PET) and ex vivo autoiadiography. Results: ELISA analysis of Tris-buffered saline brain extracts demonstrated a 40% reduction of soluble A beta protofibrils in both RmAb158-scFv8D3- and high-dose RmAb158-treated mice, whereas there was no A beta protofibril reduction in mice treated with a low dose of RmAb158. Further, ex vivo autoradiography and PET imaging revealed diffeient brain distribution patterns of RmAb158-scFv8D3 and RmAb158, suggesting that these antibodies may affect A beta levels by different mechanisms. Conclusions: With a combination of biochemical and imaging analyses, this study demonstrates that antibodies engineered to be transported across the blood brain barrier can be used to increase the efficacy of A beta immunotherapy. This strategy may allow for decreased antibody doses and thereby reduced side effects and treatment costs.

  • 8.
    Thordardottir, Steinunn
    et al.
    Karolinska Inst, Ctr Alzheimer Res, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, S-14157 Huddinge, Sweden;Karolinska Univ Hosp Huddinge, Theme Aging, S-14186 Stockholm, Sweden.
    Rodriguez-Vieitez, Elena
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Div Translat Alzheimer Neurobiol, S-14157 Huddinge, Sweden.
    Almkvist, Ove
    Karolinska Univ Hosp Huddinge, Theme Aging, S-14186 Stockholm, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Div Translat Alzheimer Neurobiol, S-14157 Huddinge, Sweden;Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden.
    Ferreira, Daniel
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Div Clin Geriatr, S-14157 Huddinge, Sweden.
    Saint-Aubert, Laure
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Div Translat Alzheimer Neurobiol, S-14157 Huddinge, Sweden;Univ Toulouse, Toulouse NeuroImaging Ctr, INSERM, UPS, Toulouse, France.
    Kinhult-Stahlbom, Anne
    Karolinska Inst, Ctr Alzheimer Res, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, S-14157 Huddinge, Sweden;Karolinska Univ Hosp Huddinge, Theme Aging, S-14186 Stockholm, Sweden.
    Thonberg, Hakan
    Karolinska Inst, Ctr Alzheimer Res, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, S-14157 Huddinge, Sweden;Karolinska Univ Hosp Huddinge, Theme Aging, S-14186 Stockholm, Sweden.
    Scholl, Michael
    Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, S-41345 Gothenburg, Sweden;Univ Gothenburg, Dept Psychiat & Neurochem, S-41345 Gothenburg, Sweden;Lund Univ, Clin Memory Res Unit, S-21224 Malmo, Sweden.
    Westman, Eric
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Div Clin Geriatr, S-14157 Huddinge, Sweden.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksdotte, Maria
    Karolinska Univ Hosp Huddinge, Theme Aging, S-14186 Stockholm, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Div Clin Geriatr, S-14157 Huddinge, Sweden.
    Zetterberg, Henrik
    Univ Gothenburg, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Sahlgrenska Acad, S-43180 Molndal, Sweden;UCL Inst Neurol, Queen Sq, London WC1N 3BG, England;UCL, UK Dementia Res Inst, London WC1N 3BG, England;Sahlgrens Univ Hosp, Clin Neurochem Lab, S-43180 Molndal, Sweden.
    Blennow, Kaj
    Univ Gothenburg, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Sahlgrenska Acad, S-43180 Molndal, Sweden;Sahlgrens Univ Hosp, Clin Neurochem Lab, S-43180 Molndal, Sweden.
    Nordberg, Agneta
    Karolinska Univ Hosp Huddinge, Theme Aging, S-14186 Stockholm, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Div Translat Alzheimer Neurobiol, S-14157 Huddinge, Sweden.
    Graff, Caroline
    Karolinska Inst, Ctr Alzheimer Res, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, S-14157 Huddinge, Sweden;Karolinska Univ Hosp Huddinge, Theme Aging, S-14186 Stockholm, Sweden.
    Reduced penetrance of the PSEN1 H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study2018In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 10, article id 45Article in journal (Refereed)
    Abstract [en]

    Background: The range of onset ages within some PSEN1 families is wide, and a few cases of reduced penetrance of PSEN1 mutations have been reported. However, published data on reduced penetrance have been limited to clinical histories, often collected retrospectively and lacking biomarker information. We present a case of reduced penetrance of the PSEN1 H163Y mutation in a carrier prospectively followed for 22 years.

    Methods: Two brothers (A and B), both carriers of the H163Y mutation, were followed between 1995 and 2017. They underwent repeated clinical evaluations, neuropsychological assessments, and cerebrospinal fluid analyses, as well as brain imaging examinations with structural magnetic resonance, [18F]fluorodeoxyglucose positron emission tomography, and [11C]Pittsburgh compound B positron emission tomography.

    Results: Brother A was followed between 44 and 64 years of age. Cognitive symptoms due to Alzheimer’s disease set in at the age of 54. Gradual worsening of symptoms resulted in admittance to a nursing home owing to dependence on others for all activities of daily living. He showed a curvilinear decline in cognitive function on neuropsychological tests, and changes on magnetic resonance imaging, positron emission tomography, and biomarkers in the cerebrospinal fluid supported a clinical diagnosis of Alzheimer’s disease. Brother A died at the age of 64 and fulfilled the criteria for definitive Alzheimer’s disease according to neuropathological examination results. Brother B was followed between the ages of 43 and 65 and showed no cognitive deterioration on repeated neuropsychological test occasions. In addition, no biomarker evidence of Alzheimer’s disease pathology was detected, either on imaging examinations or in cerebrospinal fluid.

    Conclusions: The average (SD) age of symptom onset for PSEN1 H163Y is 51 ± 7 years according to previous studies. However, we present a case of a biomarker-verified reduction in penetrance in a mutation carrier who was still symptom-free at the age of 65. This suggests that other genetic, epigenetic, and/or environmental factors modify the onset age.

  • 9.
    Wimo, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Aging Res Ctr, Stockholm, Sweden.;Stockholm Univ, Stockholm, Sweden.;Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Neurogeriatr, Stockholm, Sweden..
    Jonsson, Linus
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Aging Res Ctr, Stockholm, Sweden.;Stockholm Univ, Stockholm, Sweden..
    Fratiglioni, Laura
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Neurogeriatr, Stockholm, Sweden..
    Sandman, Per Olof
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Caring Sci, Stockholm, Sweden.;Umea Univ, Dept Nursing, Umea, Sweden.;Lulea Univ Technol, Dept Hlth Sci, Lulea, Sweden..
    Gustavsson, Anders
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Aging Res Ctr, Stockholm, Sweden.;Stockholm Univ, Stockholm, Sweden..
    Skoldunger, Anders
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Neurogeriatr, Stockholm, Sweden..
    Johansson, Lennarth
    Stockholm Gerontol Res Ctr, Stockholm, Sweden..
    The societal costs of dementia in Sweden 2012-relevance and methodological challenges in valuing informal care2016In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 8, article id 59Article in journal (Refereed)
    Abstract [en]

    Background: In this study, we sought to estimate the societal cost of illness in dementia in Sweden in 2012 using different costing approaches to highlight methodological issues. Methods: We conducted a prevalence-based cost-of-illness study with a societal perspective. Results: The societal costs of dementia in Sweden in 2012 were SEK 62.9 billion (approximately (sic) 7.2 billion, approximately US$ 9.0 billion) or SEK 398,000 per person with dementia (approximately (sic) 45,000, approximately US$ 57,000). By far the most important cost item is the cost of institutional care: about 60% of the costs. In the sensitivity analysis, different quantification and costing approaches for informal care resulted in a great variation in the total societal cost, ranging from SEK 60 billion ((sic) 6.8 billion, US$ 8.6 billion) to SEK 124 billion ((sic) 14.1 billion, US$ 17.8 billion). Conclusions: The societal costs of dementia are very high. The cost per person with dementia has decreased somewhat, mainly because of de-institutionalisation. The majority of the costs occur in the social care sector, but the costing of informal care is crucial for the cost estimates.

  • 10.
    Ygland, Emil
    et al.
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurol, Getingevagen 4, S-22185 Lund, Sweden..
    van Westen, Danielle
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Diagnost Radiol, Getingevagen 4, S-22185 Lund, Sweden..
    Englund, Elisabet
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Oncol & Pathol, Solvegatan 23, S-22185 Lund, Sweden..
    Rademakers, Rosa
    Mayo Clin, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA..
    Wszolek, Zbigniew K.
    Mayo Clin, Dept Neurol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA..
    Nilsson, Karin
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurol, Getingevagen 4, S-22185 Lund, Sweden..
    Nilsson, Christer
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurol, Getingevagen 4, S-22185 Lund, Sweden..
    Waldo, Maria Landqvist
    Lund Univ, Skane Univ Hosp, Angelholm Hosp, Dept Clin Sci Lund,Memory Clin, Vastersjogatan 10, S-26282 Angelholm, Sweden..
    Alafuzoff, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Hansson, Oskar
    Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden.;Skane Univ Hosp, Memory Clin, S-20502 Malmo, Sweden..
    Gustafson, Lars
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurol, Getingevagen 4, S-22185 Lund, Sweden..
    Puschmann, Andreas
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Neurol, Getingevagen 4, S-22185 Lund, Sweden..
    Slowly progressive dementia caused by MAPT R406W mutations: longitudinal report on a new kindred and systematic review2018In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 10, article id 2Article, review/survey (Refereed)
    Abstract [en]

    Background: The MAPT c.1216C > T (p.Arg406Trp; R406W) mutation is a known cause of frontotemporal dementia with Parkinsonism linked to chromosome 17 tau with Alzheimer's disease-like clinical features. Methods: We compiled clinical data from a new Swedish kindred with R406W mutation. Seven family members were followed longitudinally for up to 22 years. Radiological examinations were performed in six family members and neuropathological examinations in three. We systematically reviewed the literature and compiled clinical, radiological, and neuropathological data on 63 previously described R406W heterozygotes and 3 homozygotes. Results: For all cases combined, the median age of onset was 56 years and the median disease duration was 13 years. Memory impairment was the most frequent symptom, behavioral disturbance and language impairment were less common, and Parkinsonism was rare. Disease progression was most often slow. The most frequent clinical diagnosis was Alzheimer's disease. R406W homozygotes had an earlier age at onset and a higher frequency of behavioral symptoms and Parkinsonism than heterozygotes. In the new Swedish kindred, a consistent imaging finding was ventromedial temporal lobe atrophy, which was evident also in early disease stages as a widening of the collateral sulcus with ensuing atrophy of the parahippocampal gyrus. Unlike previously published R406W carriers, all three autopsied patients from the novel family showed neuropathological similarities with progressive supranuclear palsy, with predominant four-repeat (exon 10+) tau isoform (4R) tauopathy and neurofibrillary tangles accentuated in the basal-medial temporal lobe. Amyloid-beta pathology was absent. Conclusions: Dominance of 4R over three-repeat (exon 10-) tau isoforms contrasts with earlier reports of R406W patients and was not sufficiently explained by the presence of H1/H2 haplotypes in two of the autopsied patients. R406W patients often show a long course of disease with marked memory deficits. Both our neuropathological results and our imaging findings revealed that the ventromedial temporal lobes were extensively affected in the disease. We suggest that this area may represent the point of origin of tau deposition in this disease with relatively isolated tauopathy.

1 - 10 of 10
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf