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LEAD SUPERVISOR: Dr Vanessa Raymont, Department of Psychiatry

Co-supervisor: Professor John Gallacher, Department of Psychiatry

 

Commercial partner: Diadem Research Ltd, London

 

The proposed project is in the field of neurodegeneration and fits within the MRC strategic theme of prevention and early detection, facilitating earlier diagnosis and improved clinical management. The project aims of improving diagnostic and prognostic accuracy in detecting early Alzheimer’s disease (AD) also fits within the strategic theme of precision medicine, as the project would facilitate targeted risk reduction and personalized drug management when disease modifying treatments are available.

The AlzoSure® Predict test is a CE-IVD marked, plasma test and has been designated as a Breakthrough Device by the FDA. The U-p53AZ biomarker is the Alzheimer’s Disease (AD) clinically-relevant conformational variant of p53 and has been demonstrated to predict AD ahead of symptomatic onset. The novel monoclonal IGM antibody (2D3A8) specifically targets this unfolded variant of p53, which is the core technology behind Diadem’s AlzoSure® Predict prognostic test. This project would aim to build on retrospective data already collected from cohorts, by collecting prospective pilot data in UK clinical cohorts. It would develop the relationship between MRC-funded DPUK Trial delivery Framework (DPUK TDF), which is establishing a clinical research cohort recruited from NHS memory clinics, and the DPUK industry partner Diadem, and test the utility and acceptability of a plasma biomarker used to identify early AD. It would also work with an existing cohort of people with a history of traumatic brain injury (TBI), via a NIHR-funded project led by Vanessa Raymont and Khalida Ismail (co-CIs). The project plan is:

  1. Conduct a systematic review and meta-analysis of observational studies of existing biomarkers of AD in at risk groups.
  2. Determine the feasibility and utility of collecting plasma for analysis with AlzoSure® Predict to predict stage of AD pathology in clinical research cohorts. The PhD student will lead the set up of the collection pathways, with the support of the existing DPUK TDF and conduct analysis of the predictive value of AlzoSure® compared to cognitive scores.

Specific Aim 1 - To conduct a study to evaluate the performance of AlzoSure® in categorizing patients into AD disease classes and stages. These participants will be recruited via the DPUK TDF and from an existing TBI cohort (led by Vanessa Raymont).

  1. Obtain qualitative participant views on the plasma collection and its predictive value.

Specific Aim 2 - To qualitatively evaluate the acceptability of AlzoSure® via patient and carer questionnaires.

3.         Identification of a subpopulation of at risk individuals to validate the prognostic ability of AlzoSure® in AD over time, compared to other existing plasma biomarkers (neurofilament light and                 phosphorylated tau-217, already being collected).

Specific Aim 3: Validation of the prognostic ability of AlzoSure® compared to existing clinical assessments. Participants will be recruited from the DPUK Great Minds cohort, which has approximately 6,000 participants with lead in data, and via the DPUK TDF.

 

Apply using course: DPhil in Psychiatry

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