Biomarker Research Group

Biofluid biomarkers increasingly play a number of different roles in drug discovery. Biomarkers of pathology identify subjects who already have the measurable effects of molecular pathology.

Recent advances in imaging, cognitive and other biomarkers now allow detection of individuals pre-clinically. Biomarkers of proximity take that assessment one step further by quantifying the imminence of clinical progression.

They may therefore offer the most relevant window of therapeutic opportunity during which the slowing of pathology would delay the onset of symptoms without including the wide heterogeneity of individuals who may be many years before clinical onset.

We better understand which changes indicate imminent clinical conversion in at-risk subjects and as such these ‘proximity’ markers allow targeting of individuals with most to gain from treatment with near certainty that they will otherwise become symptomatic within a definable time window.

Biomarkers will be important at all stages but are essential for testing therapies in individuals with pre-clinical disease. The ultimate aim of this combined approach is to find therapies that slow decline and delay clinical onset.

CSF Biomarkers and the Leonard Wolfson CSF Laboratory

CSF-based analyses are the most advanced of the biomarkers currently available in NDD. Aβ1-42 is decreased and tau and phosphorylated tau are increased in prodromal AD.

A number of novel CSF analytical techniques are in various stages of development, and show promise in improving diagnostic specificity in AD and as a means of identifying presymptomatic individuals.

People

Equipment 

The Leonard Wolfson Biomarkers Laboratory has access to a variety of high quality equipment to develop fluid biomarker studies.

Traditional methods for measuring analytes in biofluids use immunological methods and the following platforms all work on this principal.

Please contact Dr Amanda Heslegrave (Team Leader)  for more information or queries on any of the below.

Simoa HD-1 analyser

This is another platform that uses magnetic bead based technology, but at an ultrasensitive level, up to 1000x more sensitive than traditional ELISA techniques. The sensitivity is enabled by using a disc array containing femtolitre size wells so only one bead can occupy each well and be imaged giving a digital read out at low concnetrations. Quanterix the company that manufactures this platform offer a number of ready made kits including Tau and abeta, but there is also the opportunity to make your own ‘homebrew’ kits.

Mesoscale Discovery Sector Imager 6000

This platform enables us to perform sensitive ELISA assays using both ready made kits and kits we have assembled ourselves using uncoated plates. The readout is facilitated by electrodes in the bottom of the plate that are excited when antibody is bound enabling a signal to be produced and read. This is a very easy to use system and there are a number of well validated kits that we use often i.e. abeta triplex, APP alpha and beta. Ability to multiplex is there. For further info visit the Mesoscale website. 

Magpix

This platform uses magnetic bead technology with CCD imaging. Visit the Millipore website for a full list of antibody coated beads. They can put together panels for you.

Martha Foiani in our lab is the Magpix user expert.

Biological Mass Spectrometry Centre at the UCL Institute of Child Health

-in collaboration with Dr Kevin Mills and Dr Wendy Heywood

It is not always possible to measure an analyte with an antibody so we need to use other methods. One such method is mass spectrometry, specifically Selected Reaction Monitoring (SRM) which enables us to accurately measure the amount of a protein or peptide in a sample using our knowledge of peptides formed when proteins are digested and of those peptide ion masses in the mass spectrometer. If you are interested in this technique, please look at their website to get an idea of what information they need from you or contact Amanda for informal advice.