Amyloid precursor protein (APP) contributes to pathology in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis
Language: 
English
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 ?-amyloid (A?) 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.

Author(s): 
Bryson, J. Barney
Hobbs, Carl
Parsons, Michael J.
Bosch, Karen D.
Pandraud, Amelie
Walsh, Frank S.
Doherty, Patrick
Greensmith, Linda
Item Type: 
Journal Article
Publication Title: 
Human Molecular Genetics
Journal Abbreviation: 
Hum. Mol. Genet.
Publication Date: 
9/1/2012
Publication Year: 
2012
Pages: 
3871-3882
Volume: 
21
Issue: 
17
ISSN: 
1460-2083
DOI: 
10.1093/hmg/dds215
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 22678056

Turabian/Chicago Citation

J. Barney Bryson, Carl Hobbs, Michael J. Parsons, Karen D. Bosch, Amelie Pandraud, Frank S. Walsh, Patrick Doherty and Linda Greensmith. 9/1/2012. "Amyloid precursor protein (APP) contributes to pathology in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis." Human Molecular Genetics 21: 17: 3871-3882. 10.1093/hmg/dds215.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1093/hmg/dds215 | issn = 1460-2083 | volume = 21 | pages = 3871-3882 | last = Bryson | first = J. Barney | coauthors = Hobbs, Carl, Parsons, Michael J., Bosch, Karen D., Pandraud, Amelie, Walsh, Frank S., Doherty, Patrick, Greensmith, Linda | title = Amyloid precursor protein (APP) contributes to pathology in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis | journal = Human Molecular Genetics | date = 9/1/2012 | pmid = | pmc = }} </ref>