Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis.
<h4>Background</h4>Biomarkers of disease progression in amyotrophic lateral sclerosis (ALS) could support the identification of beneficial drugs in clinical trials. We aimed to test whether soluble fragments of beta-amyloid precursor protein (sAPPα and sAPPß) correlated with clinical sub...
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2011
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oai:doaj.org-article:94ad481f6bee4590b1b06b31be85e3622021-11-18T06:47:56ZSoluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis.1932-620310.1371/journal.pone.0023600https://doaj.org/article/94ad481f6bee4590b1b06b31be85e3622011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21858182/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Biomarkers of disease progression in amyotrophic lateral sclerosis (ALS) could support the identification of beneficial drugs in clinical trials. We aimed to test whether soluble fragments of beta-amyloid precursor protein (sAPPα and sAPPß) correlated with clinical subtypes of ALS and were of prognostic value.<h4>Methodology/principal findings</h4>In a cross-sectional study including patients with ALS (N = 68) with clinical follow-up data over 6 months, Parkinson's disease (PD, N = 20), and age-matched controls (N = 40), cerebrospinal fluid (CSF) levels of sAPPα a, sAPPß and neurofilaments (NfH(SMI35)) were measured by multiplex assay, Progranulin by ELISA. CSF sAPPα and sAPPß levels were lower in ALS with a rapidly-progressive disease course (p = 0.03, and p = 0.02) and with longer disease duration (p = 0.01 and p = 0.01, respectively). CSF NfH(SMI35) was elevated in ALS compared to PD and controls, with highest concentrations found in patients with rapid disease progression (p<0.01). High CSF NfH(SMI3) was linked to low CSF sAPPα and sAPPß (p = 0.001, and p = 0.007, respectively). The ratios CSF NfH(SMI35)/CSF sAPPα,-ß were elevated in patients with fast progression of disease (p = 0.002 each). CSF Progranulin decreased with ongoing disease (p = 0.04).<h4>Conclusions</h4>This study provides new CSF candidate markers associated with progression of disease in ALS. The data suggest that a deficiency of cellular neuroprotective mechanisms (decrease of sAPP) is linked to progressive neuro-axonal damage (increase of NfH(SMI35)) and to progression of disease.Petra SteinackerLubin FangJens KuhleAxel PetzoldHayrettin TumaniAlbert C LudolphMarkus OttoJohannes BrettschneiderPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e23600 (2011) |
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Medicine R Science Q Petra Steinacker Lubin Fang Jens Kuhle Axel Petzold Hayrettin Tumani Albert C Ludolph Markus Otto Johannes Brettschneider Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis. |
| description |
<h4>Background</h4>Biomarkers of disease progression in amyotrophic lateral sclerosis (ALS) could support the identification of beneficial drugs in clinical trials. We aimed to test whether soluble fragments of beta-amyloid precursor protein (sAPPα and sAPPß) correlated with clinical subtypes of ALS and were of prognostic value.<h4>Methodology/principal findings</h4>In a cross-sectional study including patients with ALS (N = 68) with clinical follow-up data over 6 months, Parkinson's disease (PD, N = 20), and age-matched controls (N = 40), cerebrospinal fluid (CSF) levels of sAPPα a, sAPPß and neurofilaments (NfH(SMI35)) were measured by multiplex assay, Progranulin by ELISA. CSF sAPPα and sAPPß levels were lower in ALS with a rapidly-progressive disease course (p = 0.03, and p = 0.02) and with longer disease duration (p = 0.01 and p = 0.01, respectively). CSF NfH(SMI35) was elevated in ALS compared to PD and controls, with highest concentrations found in patients with rapid disease progression (p<0.01). High CSF NfH(SMI3) was linked to low CSF sAPPα and sAPPß (p = 0.001, and p = 0.007, respectively). The ratios CSF NfH(SMI35)/CSF sAPPα,-ß were elevated in patients with fast progression of disease (p = 0.002 each). CSF Progranulin decreased with ongoing disease (p = 0.04).<h4>Conclusions</h4>This study provides new CSF candidate markers associated with progression of disease in ALS. The data suggest that a deficiency of cellular neuroprotective mechanisms (decrease of sAPP) is linked to progressive neuro-axonal damage (increase of NfH(SMI35)) and to progression of disease. |
| format |
article |
| author |
Petra Steinacker Lubin Fang Jens Kuhle Axel Petzold Hayrettin Tumani Albert C Ludolph Markus Otto Johannes Brettschneider |
| author_facet |
Petra Steinacker Lubin Fang Jens Kuhle Axel Petzold Hayrettin Tumani Albert C Ludolph Markus Otto Johannes Brettschneider |
| author_sort |
Petra Steinacker |
| title |
Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis. |
| title_short |
Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis. |
| title_full |
Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis. |
| title_fullStr |
Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis. |
| title_full_unstemmed |
Soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis. |
| title_sort |
soluble beta-amyloid precursor protein is related to disease progression in amyotrophic lateral sclerosis. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/94ad481f6bee4590b1b06b31be85e362 |
| work_keys_str_mv |
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