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Soluble Beta-Amyloid Precursor Protein Is Related to Disease Progression in Amyotrophic Lateral Sclerosis

Steinacker, P; Fang, LB; Kuhle, J; Petzold, A; Tumani, H; Ludolph, AC; Otto, M; (2011) Soluble Beta-Amyloid Precursor Protein Is Related to Disease Progression in Amyotrophic Lateral Sclerosis. PLoS ONE , 6 (8) , Article e23600. 10.1371/journal.pone.0023600. Green open access

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Abstract

Background: 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 (sAPPa and sAPP beta) correlated with clinical subtypes of ALS and were of prognostic value.Methodology/Principal Findings: 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 sAPP alpha a, sAPP beta and neurofilaments (NfH(SMI35)) were measured by multiplex assay, Progranulin by ELISA. CSF sAPP alpha and sAPP beta 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(SMI35) was linked to low CSF sAPP alpha and sAPP beta (p = 0.001, and p = 0.007, respectively). The ratios CSF NfH(SMI35)/CSF sAPP alpha,-beta were elevated in patients with fast progression of disease (p = 0.002 each). CSF Progranulin decreased with ongoing disease (p = 0.04).Conclusions: 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.

Type: Article
Title: Soluble Beta-Amyloid Precursor Protein Is Related to Disease Progression in Amyotrophic Lateral Sclerosis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0023600
Publisher version: http://dx.doi.org/10.1371/journal.pone.0023600
Language: English
Additional information: © 2011 Steinacker et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: MOTOR-NEURON DISEASE, CEREBROSPINAL-FLUID, MARKERS, PHOSPHOFORMS, DEGENERATION, BIOMARKERS, DISORDERS, APOPTOSIS, DIAGNOSIS, CLEAVAGE
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
URI: https://discovery.ucl.ac.uk/id/eprint/1327912
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