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Evidence for astrocytosis in ALS demonstrated by 11C(L)-deprenyl-D2 PET
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
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2007 (English)In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 255, no 1-2, 17-22 p.Article in journal (Refereed) Published
Abstract [en]

Objective: To use deuterium-substituted [11C](l)-deprenyl PET to depict astrocytosis in vivo in patients with amyotrophic lateral sclerosis (ALS). Background: In human brain, the enzyme MAO-B is primarily located in astrocytes. l-deprenyl binds to MAO-B and autoradiography with 3H-l-deprenyl has been used to map astrocytosis in vitro. Motor neuron loss in ALS is accompanied by astrocytosis and astrocytes may play an active role in the neurodegenerative process. Deuterium-substituted [11C](l)-deprenyl PET provides an opportunity to localize astrocytosis in vivo in the brain of patients with ALS. Methods: Deuterium-substituted [11C](l)-deprenyl PET was performed in seven patients with ALS and seven healthy control subjects. Results: Increased uptake rate of [11C](l)-deprenyl was demonstrated in ALS in pons and white matter. Conclusion: This study provides evidence that astrocytosis may be detected in vivo in ALS by the use of deuterium-substituted [11C](l)-deprenyl PET though further studies are needed to determine whether deuterium-substituted [11C](l)-deprenyl binding tracks disease progression and reflects astrocytosis.

Place, publisher, year, edition, pages
2007. Vol. 255, no 1-2, 17-22 p.
Keyword [en]
Amyotrophic lateral sclerosis, ALS, Motor neuron disease, Astrocytosis, PET, MAO-B, Deprenyl
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-10812DOI: 10.1016/j.jns.2007.01.057ISI: 000245849000003PubMedID: 17346749OAI: oai:DiVA.org:uu-10812DiVA: diva2:38580
Available from: 2008-02-01 Created: 2008-02-01 Last updated: 2012-03-13Bibliographically approved
In thesis
1. Search for Biomarkers in ALS and Parkinson's Disease: Positron Emission Tomography and Cerebrospinal Fluid Studies
Open this publication in new window or tab >>Search for Biomarkers in ALS and Parkinson's Disease: Positron Emission Tomography and Cerebrospinal Fluid Studies
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

New biomarkers are needed to improve knowledge about pathophysiology, in order to provide earlier correct diagnosis and to follow disease progression of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). The aim of this thesis was to find new biomarkers for these diseases.

First, increased serum levels and unchanged levels in postmortal spinal cord of vascular endothelial growth factor (VEGF) were demonstrated. VEGF was not detected in cerebrospinal fluid (CSF) in ALS. Second, increased levels of fibroblast growth factor 2 were found in the CSF and serum of ALS patients. Both studies used enzyme-linked immunoassays. Third, a proteomics method for CSF analysis was explored, based on tryptic digestion and subsequent separation and detection of the peptides by on-line liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry. ALS-specific patterns were observed. Four out of five samples were correctly assigned, but no single protein biomarker could be identified. Fourth, [11C](L)-deprenyl-D2 (DED) positron emission tomography (PET) demonstrated increased retention in the pons and white matter in ALS. DED binds to monoamino oxidase B, which in the brain is primarily located in astrocytes. Thus evidence was provided that astrocytosis may be detected in vivo in ALS.

Fifth, normal [11C]-PIB binding in five nondemented patients with PD was reported, in contrast to previous findings of increased retention in Alzheimer's disease reflecting amyloid aggregation. Finally, the combined use of fluorodeoxyglucose and L-[β 11C]-DOPA PET for the differential diagnosis of parkinsonian syndromes was evaluated. PET provided support for the clinical diagnosis in 62 out of 75 patients, and served to exclude suspected diagnoses in another five patients.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 86 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 462
Series
Keyword
amyotrophic lateral sclerosis, ALS, Parkinson’s disease, cerebrospinal fluid, positron emission tomography, vascular endothelial growth factor, fibroblast growth factor 2, proteomics, Fourier transform ion cyclotron resonance mass spectrometry, deprenyl-D2, PIB, FDG, L-[β11C]-DOPA
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-102040 (URN)978-91-554-7544-4 (ISBN)
Public defence
2009-06-13, Grönwallsalen, Ingång 70 bv, Akademiska sjukhuset, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2009-05-20 Created: 2009-04-29 Last updated: 2009-05-20Bibliographically approved

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Johansson, AndersEngler, HenryBlomquist, GunnarScott, BeritWall, AndersAquilonius, Sten-MagnusLångström, BengtAskmark, Håkan

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Johansson, AndersEngler, HenryBlomquist, GunnarScott, BeritWall, AndersAquilonius, Sten-MagnusLångström, BengtAskmark, Håkan
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Department of NeuroscienceDepartment of Medical SciencesDepartment of Oncology, Radiology and Clinical ImmunologyDepartment of PsychologySection of Nuclear Medicine and PETDepartment of Biochemistry and Organic Chemistry
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