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

Steinacker, P., Fang, L., Kuhle, J., Petzold, A., Tumani, H., Ludolph, A.C., Otto, M., Brettschneider, J.
Journal   PLoS ONE
Species  
Analytes Measured   APP
Matrix Tested   Cerebrospinal fluid (CSF)
Year   2011
Volume   6
Page Numbers  
Application   Alzheimers
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 (sAPPα and sAPPß) 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 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).

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.

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