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Biomarkers of Alzheimer's Disease

Creating an early test for Alzheimer's disease

This study aims to investigate the use of a peripheral signature to diagnose Alzheimer’s disease.

 Student in Laboratory4


Why carry out the research?

Diagnosing Alzheimer’s disease (AD) as early as possible is vital to enable effective treatment and improve the quality of life for the sufferers. The disease has a very long pre-clinical phase and is irreversible due to the limited capacity for brain repair. Little is known regarding the cause of non-familiar AD and therefore a biomarker associated with AD to aid the diagnosis and to detect progression is of great need. Current imaging and cerebral spinal fluid (CSF) analysis have shown promising signs of reliable approaches however they are too costly and invasive to be considered suitable for routine clinical practice. Initial studies, by our group, have shown that a plasma ‘signature’ of AD does exist. Moreover, biomarker studies require continuous sampling which CSF and MRI studies prove more difficult than acquiring peripheral fluids such as blood. Our aim is to identify novel protein biomarkers in human plasma by stratifying a population of subjects according to an established marker of AD pathology measured by PiB (Pittsburgh B) PET imaging.

Previous work by our group has indicated that a peripheral signature of AD pathology can be measured by examining blood samples with patients that have hippocampal atrophy (Hye et al, 2014), brain amyloid burden (Ashton et al) and Cerebrospinal fluid (CSF).

How is the research being undertaken?

The study will consist of two major phases; discovery and replication/validation. Through collaboration and in-house sample collection we have access to a number of clinical samples that we can utilise for these different phases;

Discovery Phase

Plasma is a highly complex mixture with several dynamic ranges of concentrations. Therefore, we will aim to remove the two highly abundant proteins first. This will allow the possibility of identifying low abundant proteins derived from pathological sources. To reduce the complexity we will further separate by using a method called strong cation exchange (SCX) fractionation, and measure blood proteins by mass spectrometry.

Replication/validation Phase

The putative biomarkers from the discovery phase will be brought forward to validation and replication to imitate the findings in an independent sample set using an alternative targeted assay. This will determine if the proposed biomarkers are truly of disease activity and could be used in a clinical setting. There are a number of techniques available to our group which would be ideal replication platforms, depending on the analytes in question; customised Aptamers (SomaLogic), selected monitoring reaction (SRM), enzyme-linked immunosorbent assay (ELISA) Meso Scale Discovery (MSD) and Luminex xMAP.

Where is it happening & what is the timescale?

The project is being undertaken at the main Institute of Psychiatry in the laboratories based on the 4th floor. In addition we work closely with the KCL proteomics facility based in the South wing IoP.

The discovery phase of the project is underway, and the first results of protein separation are being compiled. Once the method is established we winicholas.1.ashton@kcl.ac.ukll be applying this to clinical samples.

Who is involved?

Professor Simon Lovestone is the Chief investigator.  He is  a Visiting Academic in the Department of Old Age Psychiatry at KCL and a professor of translational neuroscience, in the Department of Psychiatry at Oxford.

Dr Abdul Hye (Co-investigator)

Nicholas Ashton (PhD Student)

The work is funded by the Butterfield Trust

 

To find out more: 

Please contact:-

Dr Abdul Hye 

abdul.1.hye@kcl.ac.uk

Nicholas Ashton

nicholas.1.ashton@kcl.ac.uk

 

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