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Andersen, Peter M.
Alternative names
Publications (10 of 178) 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: 2019-03-20Bibliographically 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: 2019-09-03Bibliographically 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: 2019-03-20Bibliographically approved
Korner, S., Kammeyer, J., Zapf, A., Kuzma-Kozakiewicz, M., Piotrkiewicz, M., Kuraszkiewicz, B., . . . Petri, S. (2019). Influence of Environment and Lifestyle on Incidence and Progress of Amyotrophic Lateral Sclerosis in A German ALS Population. Aging and Disease, 10(2), 205-216
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
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
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: 2018-11-26Bibliographically approved
Brockmann, S. J., Freischmidt, A., Oeckl, P., Müller, K., Ponna, S. K., Helferich, A. M., . . . Weishaupt, J. H. (2018). CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease by haploinsufficiency. Human Molecular Genetics, 27(4), 706-715
Open this publication in new window or tab >>CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease by haploinsufficiency
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2018 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 27, no 4, p. 706-715Article in journal (Refereed) Published
Abstract [en]

Mutations in the mitochondrially located protein CHCHD10 cause motoneuron disease by an unknown mechanism. In this study, we investigate the mutations p. R15L and p. G66V in comparison to wild-type CHCHD10 and the non-pathogenic variant p. P34S in vitro, in patient cells as well as in the vertebrate in vivo model zebrafish. We demonstrate a reduction of CHCHD10 protein levels in p. R15L and p. G66V mutant patient cells to approximately 50%. Quantitative real-time PCR revealed that expression of CHCHD10 p. R15L, but not of CHCHD10 p. G66V, is already abrogated at the mRNA level. Altered secondary structure and rapid protein degradation are observed with regard to the CHCHD10 p. G66V mutant. In contrast, no significant differences in expression, degradation rate or secondary structure of non-pathogenic CHCHD10 p. P34S are detected when compared with wild-type protein. Knockdown of CHCHD10 expression in zebrafish to about 50% causes motoneuron pathology, abnormal myofibrillar structure and motility deficits in vivo. Thus, our data show that the CHCHD10 mutations p. R15L and p. G66V cause motoneuron disease primarily based on haploinsufficiency of CHCHD10.

Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-145134 (URN)10.1093/hmg/ddx436 (DOI)000424137500011 ()29315381 (PubMedID)
Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2019-05-07Bibliographically approved
Mueller, K., Brenner, D., Weydt, P., Meyer, T., Grehl, T., Petri, S., . . . Weishaupt, J. H. (2018). Comprehensive analysis of the mutation spectrum in 301 German ALS families. Journal of Neurology, Neurosurgery and Psychiatry, 89(8), 817-827
Open this publication in new window or tab >>Comprehensive analysis of the mutation spectrum in 301 German ALS families
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2018 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 89, no 8, p. 817-827Article in journal (Refereed) Published
Abstract [en]

Objectives Recent advances in amyotrophic lateral sclerosis (ALS) genetics have revealed that mutations in any of more than 25 genes can cause ALS, mostly as an autosomal-dominant Mendelian trait. Detailed knowledge about the genetic architecture of ALS in a specific population will be important for genetic counselling but also for genotype-specific therapeutic interventions.

Methods Here we combined fragment length analysis, repeat-primed PCR, Southern blotting, Sanger sequencing and whole exome sequencing to obtain a comprehensive profile of genetic variants in ALS disease genes in 301 German pedigrees with familial ALS. We report C9orf72 mutations as well as variants in consensus splice sites and non-synonymous variants in protein-coding regions of ALS genes. We furthermore estimate their pathogenicity by taking into account type and frequency of the respective variant as well as segregation within the families.

Results 49% of our German ALS families carried a likely pathogenic variant in at least one of the earlier identified ALS genes. In 45% of the ALS families, likely pathogenic variants were detected in C9orf72, SOD1, FUS, TARDBP or TBK1, whereas the relative contribution of the other ALS genes in this familial ALS cohort was 4%. We identified several previously unreported rare variants and demonstrated the absence of likely pathogenic variants in some of the recently described ALS disease genes.

Conclusions We here present a comprehensive genetic characterisation of German familial ALS. The present findings are of importance for genetic counselling in clinical practice, for molecular research and for the design of diagnostic gene panels or genotype-specific therapeutic interventions in Europe.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2018
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-151563 (URN)10.1136/jnnp-2017-317611 (DOI)000442475000013 ()29650794 (PubMedID)
Available from: 2018-09-10 Created: 2018-09-10 Last updated: 2018-09-10Bibliographically approved
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