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VEGF is increased in serum but not in spinal cord from patients with amyotrophic lateral sclerosis
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
2002 In: NeuroReport, Vol. 13, no 17, 2199-2201 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2002. Vol. 13, no 17, 2199-2201 p.
Identifiers
URN: urn:nbn:se:uu:diva-92661OAI: oai:DiVA.org:uu-92661DiVA: diva2:165823
Available from: 2005-03-17 Created: 2005-03-17Bibliographically approved
In thesis
1. ALS – a Clinical Thesis
Open this publication in new window or tab >>ALS – a Clinical Thesis
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Amyotrophic lateral sclerosis (ALS) is characterized by a progressive loss of upper and lower motor neurons, resulting in muscle weakness and death from respiratory failure within 3-5 years after onset. The incidence is 1.5-2.7/100,000 inhabitants. 5-10% of all cases are hereditary. The aetiology of sporadic ALS is still unknown.

The only neuroprotective drug approved for the treatment of ALS is riluzole, a glutamate-antagonist, which has shown to improve survival. We evaluated if riluzole sales statistics can be used as a method for estimating the prevalence of ALS/motor neuron disease in Sweden. We found that this method, which is less time consuming than conventional methods, could be used as a crude marker for the prevalence.

In a longitudinal study of overall Quality of Life (QoL) in ALS we found that QoL changes only slightly over time despite disease progression. ALS does not necessarily result in a low QoL.

Growth factors are important for the survival of neurons. In ALS we found increased or normal levels of GDNF mRNA and BDNF mRNA in muscle biopsies, VEGF in serum and spinal cord and FGF-2 in serum and cerebrospinal fluid. There is thus no deficit of these growth factors although there may be a relative lack because of high demands of the motor neurons. Polyamines are small aliphatic molecules that are important for the function of cells. The level of the polyamines spermidine and spermine were increased in red blood cells in both patients with ALS and patients with Parkinson’s disease, suggesting that polyamines may have a role for the neurodegenerative process. Polyamines in spinal cord were of the same level in the patients with ALS and in controls, indicating a maintained regulation of polyamines at the end-stage of the disease.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 61 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 12
Keyword
Neurosciences, ALS, epidemiology, drug sales statistics, QoL, growth factors, polyamines, Neurovetenskap
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-4804 (URN)91-554-6157-3 (ISBN)
Public defence
2005-04-08, Hedstrandsalen, Akademiska sjukhuset, Uppsala, 13:15
Opponent
Supervisors
Available from: 2005-03-17 Created: 2005-03-17Bibliographically approved
2. 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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