Teacher:In this task, you are given an abstract of article. Your task is to generate label "True" if abstract is structured, otherwise generate "False". A structured abstract is composed of a topic sentence (or key sentence), relevant supporting sentences, and a closing (or transition) sentence. This structure is key to keeping your abstract focused on the main idea and creating a clear and concise image.
Teacher: Now, understand the problem? Solve this instance: INTRODUCTION The -secretase enzyme, -site amyloid precursor protein-cleaving enzyme 1 (BACE1), cleaves amyloid precursor protein (APP) in the first step in -amyloid (A) peptide production. Thus, BACE1 is a key target for candidate disease-modifying treatment of Alzheimer's disease. In a previous exploratory A biomarker study, we found that BACE1 inhibitor treatment resulted in decreased levels of A1-34 together with increased A5-40, suggesting that these A species may be novel pharmacodynamic biomarkers in clinical trials. We have now examined whether the same holds true in humans.
METHODS In an investigator-blind, placebo-controlled and randomized study, healthy subjects (n =18) were randomly assigned to receive a single dose of 30 mg of LY2811376 (n =6), 90 mg of LY2811376 (n =6), or placebo (n =6). We used hybrid immunoaffinity-mass spectrometry (HI-MS) and enzyme-linked immunosorbent assays to monitor a variety of A peptides.
RESULTS Here, we demonstrate dose-dependent changes in cerebrospinal fluid (CSF) A1-34, A5-40 and A5-X after treatment with the BACE1-inhibitor LY2811376. A5-40 and A5-X increased dose-dependently, as reflected by two independent methods, while A1-34 dose-dependently decreased.
CONCLUSION Using HI-MS for the first time in a study where subjects have been treated with a BACE inhibitor, we confirm that CSF A1-34 may be useful in clinical trials on BACE1 inhibitors to monitor target engagement. Since it is less hydrophobic than longer A species, it is less susceptible to preanalytical confounding factors and may thus be a more stable marker. By independent measurement techniques, we also show that BACE1 inhibition in humans is associated with APP-processing into N-terminally truncated A peptides via a BACE1-independent pathway.
TRIAL REGISTRATION ClinicalTrials.gov NCT00838084. Registered: First received: January 23, 2009, Last updated: July 14, 2009, Last verified: July 2009.
Student:
True