Metabolic profiling of a transgenic Caenorhabditis elegans Alzheimer model

Abstract

Despite decades of research, no early-onset biomarkers are currently available for Alzheimer's disease, a cureless neurodegenerative disease afflicting millions worldwide. In this study, transgenic Caenorhabditis elegans were used to investigate changes in the metabolome after induced expression of amyloid-β. GC- and LC-MS-based platforms determined a total of 157 differential features. Some of these were identified using in-house (GC-MS) or public libraries (LC-MS), revealing changes in allantoin, cystathionine and tyrosine levels. Since C. elegans is far better suited to metabolomics studies than most other model systems, the accordance of these findings with vertebrate literature is promising and argues for further use of C. elegans as a model of human pathology in the study of AD.

Keywords: Alzheimer’s disease; Amyloid-β; Caenorhabditis elegans; Metabolic profiling; Metabolomics.

Fig. 1

Scheme of experimental setup. Both AD model and control strains were cultured for 34 h at 16 °C. After this period, a temperature upshift to 23 °C was performed, inducing amyloid-β₄₂ expression in the AD strain only. Thirty hours later, worms were collected and snap frozen with liquid nitrogen. An 80 % ice-cold methanol extraction was performed and samples were aliquoted for GC–MS, RP-QTOF or ANP-QTOF. A After data-analysis, features that were putatively identified showed a similar pattern as seen in previous human AD research. B Some of our unidentified features could be linked to LC–MS AD metabolomics profiling literature

Fig. 2

Representative UPLC ESI-base peak chromatograms of C. elegans extracts from different platforms. X-axis: Retention time (from 0 to 14 min), Y axis: Peak intensity (total ion count from 0 to 8.0E6)