Mass spectrometry technique shown to improve detection of Alzheimer’s disease biomarkers

Written by Sarah Jones, Future Science Group

The detection of tau-derived peptides has been dramatically improved through the use of an innovative MS workflow. These peptides are directly related to human Alzheimer’s pathology and can be used as early stage biomarkers of the disease. The peer-reviewed study was led by Proteome Sciences plc (Cobham, UK) alongside a group of highly respected universities and hospitals.

The collaborative study applied the TMTcalibrator workflow to analyse cerebrospinal fluid and detect phosphorylated tau and other disease related biomarkers with a high level sensitivity. The results were recently published online in the Journal of Alzheimer’s Disease.

The TMTcalibrator workflow demonstrated unparalleled levels of sensitivity in the detection of tissue-derived biomarkers by combining the analysis of diseased tissue and body fluids. In this study, which is the first to be published using the TMTcalibrator, the detection of 47 tau phosphopeptides covering 31 clinically-relevant phosphorylation sites is reported. Coverage of 76.8% of human tau in CSF was achieved.

The use of MS to profile phosphorylated tau in CSF has previously been limited to very few sites and based on a prior selection of targets. The detection of different phosphopeptides in an unbiased manner is allowed by this workflow.

Commenting on the study, Ian Pike, Chief Scientific Officer at Proteome Sciences elaborated, “This study clearly demonstrates the potential of combined tissue and fluid proteomics to discover and validate low abundant, tissue-derived biomarkers in peripheral fluids, which in this case resulted in the widest coverage of both tau and phosphorylated tau in human cerebrospinal fluid.

“Many of the tau peptides showed strong regulation in the three Alzheimer’s patients relative to three controls, and these may offer a means to earlier and more accurate diagnosis of the disease in the future.” Pike continued.

This study, as well as providing a detailed profiling of CSF tau, has produced data on 100 other regulated proteins, several whose genes carry mutations that increase the risk of Alzheimer’s disease.

Sources: Russell CL, Mitra V, Hansson K et al. Comprehensive Quantitative Profiling of Tau and Phosphorylated Tau Peptides in Cerebrospinal Fluid by Mass Spectrometry Provides New Biomarker Candidates. J. Alzheimers Dis. Preprint, 1-11 (2016);