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

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 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 sAPPa a, sAPPß and neurofilaments (NfH SMI35) were measured by multiplex assay, Progranulin by ELISA. CSF sAPPa 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 sAPPa and sAPPß (p = 0.001, and p = 0.007, respectively). The ratios CSF NfH SMI35 /CSF sAPPa,-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-axona

Nocturnal hypoxia in motor neuron disease is not predicted by standard respiratory function tests

Background: With increasing awareness of motor neuron disease (MND) in Australia, the approach to respiratory management of patients with this disease will more commonly face the respiratory physician. Aim: The aim of this study was to determine if standard respiratory function tests could determine the presence of nocturnal hypoxia (NH) in patients with MND. Methods: Respiratory function tests were used to examine daytime respiratory function, and sleep studies were used to detect NH in 16 consecutive patients with MND and in 9 healthy control subjects. Demographic data, clinical parameters, respiratory function tests and sleep studies were obtained. Statistical analyses were carried out using t-tests and anova, where appropriate. Results: NH was detected in 50% of patients with MND, with no hypoxic events detected in the control group. Standard respiratory function tests were not able to predict the presence of NH. Conclusion: There was no correlation between respiratory function tests and NH. This study emphasizes the inability of standard respiratory function tests to predict NH that may arise early in the course of MND.4 page(s