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Amyloid precursor protein (APP) contributes to pathology in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis.
Hum Mol Genet. 2012 Sep 01; 21(17):3871-82.HM

Abstract

In amyotrophic lateral sclerosis (ALS), the progressive loss of motor neurons is accompanied by extensive muscle denervation, resulting in paralysis and ultimately death. Upregulation of amyloid beta (A4) precursor protein (APP) in muscle fibres coincides with symptom onset in both sporadic ALS patients and the SOD1(G93A) mouse model of familial ALS. We have further characterized this response in SOD1(G93A) mice and also revealed elevated levels of β-amyloid (Aβ) peptides in the SOD1(G93A) spinal cord, which were predominantly localized within motor neurons and their surrounding glial cells. We therefore examined the effect of genetic ablation of APP on disease progression in SOD1(G93A) mice, which significantly improved multiple disease parameters, including innervation, motor function, muscle contractile characteristics, motor unit and motor neuron survival. These results therefore strongly suggest that APP actively contributes to SOD1(G93A)-mediated pathology. Together with observations from ALS cases, this study indicates that APP may contribute to human ALS pathology.

Authors+Show Affiliations

Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22678056

Citation

Bryson, J Barney, et al. "Amyloid Precursor Protein (APP) Contributes to Pathology in the SOD1(G93A) Mouse Model of Amyotrophic Lateral Sclerosis." Human Molecular Genetics, vol. 21, no. 17, 2012, pp. 3871-82.
Bryson JB, Hobbs C, Parsons MJ, et al. Amyloid precursor protein (APP) contributes to pathology in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Hum Mol Genet. 2012;21(17):3871-82.
Bryson, J. B., Hobbs, C., Parsons, M. J., Bosch, K. D., Pandraud, A., Walsh, F. S., Doherty, P., & Greensmith, L. (2012). Amyloid precursor protein (APP) contributes to pathology in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Human Molecular Genetics, 21(17), 3871-82. https://doi.org/10.1093/hmg/dds215
Bryson JB, et al. Amyloid Precursor Protein (APP) Contributes to Pathology in the SOD1(G93A) Mouse Model of Amyotrophic Lateral Sclerosis. Hum Mol Genet. 2012 Sep 1;21(17):3871-82. PubMed PMID: 22678056.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amyloid precursor protein (APP) contributes to pathology in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis. AU - Bryson,J Barney, AU - Hobbs,Carl, AU - Parsons,Michael J, AU - Bosch,Karen D, AU - Pandraud,Amelie, AU - Walsh,Frank S, AU - Doherty,Patrick, AU - Greensmith,Linda, Y1 - 2012/06/07/ PY - 2012/6/9/entrez PY - 2012/6/9/pubmed PY - 2012/12/15/medline SP - 3871 EP - 82 JF - Human molecular genetics JO - Hum Mol Genet VL - 21 IS - 17 N2 - In amyotrophic lateral sclerosis (ALS), the progressive loss of motor neurons is accompanied by extensive muscle denervation, resulting in paralysis and ultimately death. Upregulation of amyloid beta (A4) precursor protein (APP) in muscle fibres coincides with symptom onset in both sporadic ALS patients and the SOD1(G93A) mouse model of familial ALS. We have further characterized this response in SOD1(G93A) mice and also revealed elevated levels of β-amyloid (Aβ) peptides in the SOD1(G93A) spinal cord, which were predominantly localized within motor neurons and their surrounding glial cells. We therefore examined the effect of genetic ablation of APP on disease progression in SOD1(G93A) mice, which significantly improved multiple disease parameters, including innervation, motor function, muscle contractile characteristics, motor unit and motor neuron survival. These results therefore strongly suggest that APP actively contributes to SOD1(G93A)-mediated pathology. Together with observations from ALS cases, this study indicates that APP may contribute to human ALS pathology. SN - 1460-2083 UR - https://www.unboundmedicine.com/medline/citation/22678056/Amyloid_precursor_protein__APP__contributes_to_pathology_in_the_SOD1_G93A__mouse_model_of_amyotrophic_lateral_sclerosis_ L2 - https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/dds215 DB - PRIME DP - Unbound Medicine ER -