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UCL Institute of Neurology, Queen Square

3 ARTICLES PUBLISHED IN JoVE

Medicine

A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status

Wendy E. Heywood^*1, Anna Baud^*1, Emily Bliss¹, Ernestas Sirka¹, Jonathan M. Schott², Henrik Zetterberg³, Daniela Galimberti⁴, Neil J. Sebire⁵, Kevin Mills¹

¹Centre for Translational Omics, Genetics and Genomic Medicine Deptartment, Great Ormond Street Institute of Child Health, University College London, ²Dementia Research Centre, Institute of Neurology, University College London, ³Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, ⁴Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, ⁵Great Ormond Street Hospital for Children, University College London

We describe a high-throughput, multiplex, and targeted proteomic cerebrospinal fluid (CSF) assay developed with potential for clinical translation. The test can quantitate potential markers and risk factors for neurodegeneration, such as the apolipoprotein E variants (E2, E3 and E4), and measure their allelic expression.

Medicine

Absolute Quantification of Aβ_1-42 in CSF Using a Mass Spectrometric Reference Measurement Procedure

Josef Pannee^1,2, Kaj Blennow^1,2, Henrik Zetterberg^1,2,3, Erik Portelius^1,2

¹Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, ²Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, ³UCL Institute of Neurology, Queen Square

A reference measurement procedure for the absolute quantification of Aβ_1-42 in human CSF based on solid-phase extraction and liquid chromatography tandem mass spectrometry is described.

Neuroscience

Sample Preparation for Endopeptidomic Analysis in Human Cerebrospinal Fluid

Karl T. Hansson¹, Tobias Skillbäck^1,2, Elin Pernevik¹, Jessica Holmén-Larsson¹, Gunnar Brinkmalm¹, Kaj Blennow^1,2, Henrik Zetterberg^1,2,3, Johan Gobom^1,2

¹Inst. of Neuroscience and Physiology, Dept. of Psychiatry and Neurochemistry, Sahlgrenska Academy at University of Gothenburg, ²Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, ³Department of Molecular Neuroscience, UCL Institute of Neurology

A method for mass spectrometric analysis of endogenous peptides in human cerebrospinal fluid (CSF) is presented. By employing molecular weight cut-off filtration, chromatographic pre-fractionation, mass spectrometric analysis and a subsequent combination of peptide identification strategies, it was possible to expand the known CSF peptidome nearly ten-fold compared to previous studies.