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Andersen, Peter M.
Alternative names
Publications (10 of 181) Show all publications
Miltenberger-Miltenyi, G., Conceicao, V. A., Gromicho, M., Pronto-Laborinho, A. C., Pinto, S., Andersen, P. M. & de Carvalho, M. (2019). C9orf72 expansion is associated with accelerated decline of respiratory function and decreased survival in amyotrophic lateral sclerosis [Letter to the editor]. Journal of Neurology, Neurosurgery and Psychiatry, 90(1), 118-120
Open this publication in new window or tab >>C9orf72 expansion is associated with accelerated decline of respiratory function and decreased survival in amyotrophic lateral sclerosis
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2019 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 90, no 1, p. 118-120Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-157235 (URN)10.1136/jnnp-2018-318032 (DOI)000459181800022 ()29661924 (PubMedID)
Available from: 2019-03-20 Created: 2019-03-20 Last updated: 2019-11-19Bibliographically approved
Miltenberger-Miltenyi, G., Conceicao, V. A., Gromicho, M., Pronto-Laborinho, A. C., Pinto, S., Andersen, P. M. & De Carvalho, M. (2019). C9orf72 expansion is associated with accelerated decline of respiratory function and decreased survival in amyotrophic lateral sclerosis. Paper presented at 22nd Annual Meeting of the Portuguese-Society-of-Human-Genetics (SPGH), NOV 15-17, 2018, Porto, PORTUGAL. Medicine (Baltimore, Md.), 98(26)
Open this publication in new window or tab >>C9orf72 expansion is associated with accelerated decline of respiratory function and decreased survival in amyotrophic lateral sclerosis
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2019 (English)In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 98, no 26Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2019
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-162893 (URN)000480733400159 ()
Conference
22nd Annual Meeting of the Portuguese-Society-of-Human-Genetics (SPGH), NOV 15-17, 2018, Porto, PORTUGAL
Note

Meeting Abstract: P6

Available from: 2019-09-03 Created: 2019-09-03 Last updated: 2019-11-19Bibliographically approved
Oeckl, P., Weydt, P., Steinacker, P., Anderl-Straub, S., Nordin, F., Volk, A. E., . . . Otto, M. (2019). Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase. Journal of Neurology, Neurosurgery and Psychiatry, 90(1), 4-10
Open this publication in new window or tab >>Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase
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2019 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 90, no 1, p. 4-10Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate the role of neuroinflammation in asymptomatic and symptomatic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mutation carriers.

Methods: The neuroinflammatory markers chitotriosidase 1 (CHIT1), YKL-40 and glial fibrillary acidic protein (GFAP) were measured in cerebrospinal fluid (CSF) and blood samples from asymptomatic and symptomatic ALS/FTD mutation carriers, sporadic cases and controls by ELISA.

Results: CSF levels of CHIT1, YKL-40 and GFAP were unaffected in asymptomatic mutation carriers (n=16). CHIT1 and YKL-40 were increased in gALS (p<0.001, n=65) whereas GFAP was not affected. Patients with ALS carrying a CHIT1 polymorphism had lower CHIT1 concentrations in CSF (-80%) whereas this polymorphism had no influence on disease severity. In gFTD (n=23), increased YKL-40 and GFAP were observed (p<0.05), whereas CHIT1 was nearly not affected. The same profile as in gALS and gFTD was observed in sALS (n=64/70) and sFTD (n=20/26). CSF and blood concentrations correlated moderately (CHIT1, r=0.51) to weak (YKL-40, r=0.30, GFAP, r=0.39). Blood concentrations of these three markers were not significantly altered in any of the groups except CHIT1 in gALS of the Ulm cohort (p<0.05).

Conclusion: Our data indicate that neuroinflammation is linked to the symptomatic phase of ALS/FTD and shows a similar pattern in sporadic and genetic cases. ALS and FTD are characterised by a different neuroinflammatory profile, which might be one driver of the diverse presentations of the ALS/FTD syndrome.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-157233 (URN)10.1136/jnnp-2018-318868 (DOI)000459181800004 ()30224549 (PubMedID)
Available from: 2019-03-20 Created: 2019-03-20 Last updated: 2019-11-19Bibliographically approved
diva2:1316869
Open this publication in new window or tab >>Influence of Environment and Lifestyle on Incidence and Progress of Amyotrophic Lateral Sclerosis in A German ALS Population
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2019 (English)In: Aging and Disease, ISSN 2152-5250, Vol. 10, no 2, p. 205-216Article in journal (Refereed) Published
Abstract [en]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease mainly affecting upper and lower motor neurons in the brain and spinal cord. Pathogenesis of ALS is still unclear, and a multifactorial etiology is presumed. The remarkable clinical heterogeneity between different phenotypes of ALS patients suggests that environmental and lifestyle factors could play a role in onset and progression of ALS. We analyzed a cohort of 117 ALS patients and 93 controls. ALS patients and controls were compared regarding physical activity, dietary habits, smoking, residential environment, potentially toxic environmental factors and profession before symptom onset and throughout the disease course. Data were collected by a personal interview. For statistical analysis descriptive statistics, statistical tests and analysis of variance were used. ALS patients and controls did not differ regarding smoking, diet and extent of physical training. No higher frequency of toxic influences could be detected in the ALS group. ALS patients lived in rural environment considerably more often than the control persons, but this was not associated with a higher percentage of occupation in agriculture. There was also a higher percentage of university graduates in the ALS group. Patients with bulbar onset were considerably more often born in an urban environment as compared to spinal onset. Apart from education and environment, ALS phenotypes did not differ in any investigated environmental or life-style factor. The rate of disease progression was not influenced by any of the investigated environmental and life-style factors. The present study could not identify any dietary habit, smoking, physical activity, occupational factor as well as toxic influences as risk factor or protective factor for onset or progression of ALS. Living in rural environment and higher education might be associated with higher incidence of ALS.

Place, publisher, year, edition, pages
Fort Worth: International Society on Aging & Disease, 2019
Keywords
ALS, environment, life-style, epidemiology, phenotypes
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-158731 (URN)10.14336/AD.2018.0327 (DOI)000463718400001 ()
Available from: 2019-05-21 Created: 2019-05-21 Last updated: 2019-05-21Bibliographically approved
Forsberg, K., Graffmo, K. S., Pakkenberg, B., Weber, M., Nielsen, M., Marklund, S. L., . . . Munch Andersen, P. (2019). Misfolded SOD1 inclusions in patients with mutations in C9orf72 and other ALS/FTD-associated genes. Journal of Neurology, Neurosurgery and Psychiatry, 90(8), 861-869
Open this publication in new window or tab >>Misfolded SOD1 inclusions in patients with mutations in C9orf72 and other ALS/FTD-associated genes
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2019 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 90, no 8, p. 861-869Article in journal (Refereed) Published
Abstract [en]

Objective: A hallmark of amyotrophic lateral sclerosis (ALS) caused by mutations in superoxide dismutase-1 (SOD1) are inclusions containing SOD1 in motor neurons. Here, we searched for SOD1-positive inclusions in 29 patients carrying ALS-linked mutations in six other genes.

Methods: A panel of antibodies that specifically recognise misfolded SOD1 species were used for immunohistochemical investigations of autopsy tissue.

Results: The 18 patients with hexanucleotide-repeat-expansions in C9orf72 had inclusions of misfolded wild type (WT) SOD1(WT) in spinal motor neurons. Similar inclusions were occasionally observed in medulla oblongata and in the motor cortex and frontal lobe. Patients with mutations in FUS, KIF5A, NEK1, ALSIN or VAPB, carried similar SOD1(WT) inclusions. Minute amounts of misSOD1(WT) inclusions were detected in 2 of 20 patients deceased from non-neurological causes and in 4 of 10 patients with other neurodegenerative diseases. Comparison was made with 17 patients with 9 different SOD1 mutations. Morphologically, the inclusions in patients with mutations in C9orf72HRE, FUS, KIF5A, NEK1, VAPB and ALSIN resembled inclusions in patients carrying the wildtype-like SOD1(D90A) mutation, whereas patients carrying unstable SOD1 mutations (A4V, V5M, D76Y, D83G, D101G, G114A, G127X, L144F) had larger skein-like SOD1-positive inclusions.

Conclusions and relevance Abundant inclusions containing misfolded SOD1(WT) are found in spinal and cortical motor neurons in patients carrying mutations in six ALS-causing genes other than SOD1. This suggests that misfolding of SOD1(WT) can be part of a common downstream event that may be pathogenic. The new anti-SOD1 therapeutics in development may have applications for a broader range of patients.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
Keywords
amyotrophic lateral sclerosis, neuronal inclusions, C9orf72, KIF5A, superoxide dismutase-1
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-163689 (URN)10.1136/jnnp-2018-319386 (DOI)000482509400004 ()30992335 (PubMedID)
Available from: 2019-10-17 Created: 2019-10-17 Last updated: 2019-10-17Bibliographically approved
Brännström, T., Andersen, P. M., Bergh, J., Ekhtiari Bidhendi, E. & Marklund, S. M. (2019). Mutant SOD1 aggregates from human ventral horn transmit templated aggregation and fatal ALS-like disease. Paper presented at 19th International Congress of Neuropathology, SEP 23-27, 2018, Tokyo, JAPAN. Brain Pathology, 29, 90-90
Open this publication in new window or tab >>Mutant SOD1 aggregates from human ventral horn transmit templated aggregation and fatal ALS-like disease
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2019 (English)In: Brain Pathology, ISSN 1015-6305, E-ISSN 1750-3639, Vol. 29, p. 90-90Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
John Wiley & Sons, 2019
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-157592 (URN)000459814800279 ()
Conference
19th International Congress of Neuropathology, SEP 23-27, 2018, Tokyo, JAPAN
Note

Supplement: 1

Special Issue: SI

Meeting Abstract: P2-66

Available from: 2019-03-28 Created: 2019-03-28 Last updated: 2019-03-28Bibliographically approved
Benatar, M., Wuu, J., Lombardi, V., Jeromin, A., Bowser, R., Andersen, P. M. & Malaspina, A. (2019). Neurofilaments in pre-symptomatic ALS and the impact of genotype. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 20(7-8), 538-548
Open this publication in new window or tab >>Neurofilaments in pre-symptomatic ALS and the impact of genotype
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2019 (English)In: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 20, no 7-8, p. 538-548Article in journal (Refereed) Published
Abstract [en]

Objective. To evaluate serum and cerebrospinal fluid (CSF) levels of phosphorylated neurofilament heavy (pNfH), and to compare these to levels of neurofilament light (NfL), as biomarkers of pre-symptomatic ALS. Design. The study population includes 34 controls, 79 individuals at-risk for ALS, 22 ALS patients, and 14 phenoconverters. At-risk individuals are enrolled through Pre-Symptomatic Familial ALS (Pre-fALS), a longitudinal natural history and biomarker study of individuals who are carriers of any ALS-associated gene mutation, but who demonstrate no clinical evidence of disease at the time of enrollment. pNfH and NfL in serum and CSF were quantified using established enzyme-linked immunosorbent assays. Results. There is a longitudinal increase in serum pNfH in advance of the emergence of clinically manifest ALS. A similar pattern is observed for NfL, but with the absolute levels also frequently exceeding a normative threshold. Although CSF data are more sparse, similar patterns are observed for both neurofilaments, with absolute levels exceeding a normative threshold prior to phenoconversion. In serum, these changes are observed in the 6-12 months prior to disease among SOD1 A4V mutation carriers, and as far back as 2 and 3.5 years, respectively, in individuals with a FUS c.521del6 mutation and a C9ORF72 hexanucleotide repeat expansion. Conclusions. Serum and CSF pNfH increase prior to phenoconversion. In CSF, the temporal course of these changes is similar to NfL. In serum, however, pNfH is less sensitive to pre-symptomatic disease than NfL. The duration of pre-symptomatic disease, as defined by changes in neurofilaments, may vary depending on underlying genotype.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Amyotrophic lateral sclerosis, neurofilaments, biomarkers, pre-symptomatic, disease prevention
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:umu:diva-163682 (URN)10.1080/21678421.2019.1646769 (DOI)000482522900001 ()30892087 (PubMedID)
Available from: 2019-10-21 Created: 2019-10-21 Last updated: 2019-10-21Bibliographically approved
Andersen, P. M., Hempel, M., Santer, R., Nordström, U., Tsiakas, K., Johannsen, J., . . . Marklund, S. L. (2019). Phenotype in an Infant with SOD1 Homozygous Truncating Mutation [Letter to the editor]. New England Journal of Medicine, 381(5), 486-488
Open this publication in new window or tab >>Phenotype in an Infant with SOD1 Homozygous Truncating Mutation
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2019 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 381, no 5, p. 486-488Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Massachusetts Medical Society, 2019
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-162395 (URN)10.1056/NEJMc1905039 (DOI)000478064200016 ()31314961 (PubMedID)
Available from: 2019-08-20 Created: 2019-08-20 Last updated: 2019-08-20Bibliographically approved
Keskin, I., Forsgren, E., Lehmann, M., Andersen, P. M., Brännström, T., Lange, D. J., . . . Gilthorpe, J. D. (2019). The molecular pathogenesis of superoxide dismutase 1-linked ALS is promoted by low oxygen tension. Acta Neuropathologica, 138(1), 85-101
Open this publication in new window or tab >>The molecular pathogenesis of superoxide dismutase 1-linked ALS is promoted by low oxygen tension
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2019 (English)In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 138, no 1, p. 85-101Article in journal (Refereed) Published
Abstract [en]

Mutations in superoxide dismutase 1 (SOD1) cause amyotrophic lateral sclerosis (ALS). Disease pathogenesis is linked to destabilization, disorder and aggregation of the SOD1 protein. However, the non-genetic factors that promote disorder and the subsequent aggregation of SOD1 have not been studied. Mainly located to the reducing cytosol, mature SOD1 contains an oxidized disulfide bond that is important for its stability. Since O2 is required for formation of the bond, we reasoned that low O2 tension might be a risk factor for the pathological changes associated with ALS development. By combining biochemical approaches in an extensive range of genetically distinct patient-derived cell lines, we show that the disulfide bond is an Achilles heel of the SOD1 protein. Culture of patient-derived fibroblasts, astrocytes, and induced pluripotent stem cell-derived mixed motor neuron and astrocyte cultures (MNACs) under low oxygen tensions caused reductive bond cleavage and increases in disordered SOD1. The effects were greatest in cells derived from patients carrying ALS-linked mutations in SOD1. However, significant increases also occurred in wild-type SOD1 in cultures derived from non-disease controls, and patients carrying mutations in other common ALS-linked genes. Compared to fibroblasts, MNACs showed far greater increases in SOD1 disorder and even aggregation of mutant SOD1s, in line with the vulnerability of the motor system to SOD1-mediated neurotoxicity. Our results show for the first time that O2 tension is a principal determinant of SOD1 stability in human patient-derived cells. Furthermore, we provide a mechanism by which non-genetic risk factors for ALS, such as aging and other conditions causing reduced vascular perfusion, could promote disease initiation and progression.

Place, publisher, year, edition, pages
New York: Springer, 2019
Keywords
Amyotrophic lateral sclerosis (ALS), Superoxide dismutase 1 (SOD1), Disulfide bond, Oxygen tension, Protein disorder, Protein aggregation, Patient-derived cells
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-157037 (URN)10.1007/s00401-019-01986-1 (DOI)000471708700005 ()30863976 (PubMedID)
Funder
Swedish Research Council, VRMH 2015-02804Knut and Alice Wallenberg Foundation, 2012.0091Västerbotten County CouncilThe Kempe FoundationsThe Swedish Brain Foundation, Hjarnfonden FO2015-0234
Note

Originally included in thesis in manuscript form.

Available from: 2019-03-06 Created: 2019-03-06 Last updated: 2019-07-12Bibliographically approved
Canosa, A., De Marco, G., Lomartire, A., Rinaudo, M. T., Di Cunto, F., Turco, E., . . . Chio, A. (2018). A novel p.Ser108LeufsTer15 SOD1 mutation leading to the formation of a premature stop codon in an apparently sporadic ALS patient: insights into the underlying pathomechanisms. Neurobiology of Aging, 72
Open this publication in new window or tab >>A novel p.Ser108LeufsTer15 SOD1 mutation leading to the formation of a premature stop codon in an apparently sporadic ALS patient: insights into the underlying pathomechanisms
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2018 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 72Article in journal (Refereed) Published
Abstract [en]

We report an apparently sporadic amyotrophic lateral sclerosis patient carrying a heterozygous novel frameshift SOD1 mutation (p.Ser108LeufsTer15), predicted to cause a premature protein truncation. RTPCR analysis of SOD1 mRNA and SDS-PAGE/Western blot analysis of PBMC demonstrated that mRNA from the mutant allele is expressed at levels similar to those of the wild-type allele, but the truncated protein is undetectable also in the insoluble fraction and after proteasome inhibition. Accordingly, the dismutation activity in erythrocytes is halved. Thus, the pathogenic mechanism associated with this mutation might be based on an insufficient activity of SOD1 that would make motor neurons more vulnerable to oxidative injury. However, it cannot be excluded that p.Ser108LeufsTer15 SOD1 is present in the nervous tissue and, being less charged and hence having less repulsive forces than the wild-type protein, may trigger toxic mechanisms as a consequence of its propensity to aggregate. 

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Amyotrophic lateral sclerosis, SOD1, Truncated protein, Frameshift mutation, Oxidative stress, Protein aggregation
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-153540 (URN)10.1016/j.neurobiolaging.2018.08.014 (DOI)000449073700028 ()30236613 (PubMedID)
Available from: 2018-11-26 Created: 2018-11-26 Last updated: 2019-11-19Bibliographically approved
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