Blood based diagnostic biomarkers for Dementia with Lewy Bodies

  • Research type

    Research Study

  • Full title

    Discovery of blood-based diagnostic biomarkers for dementia with Lewy bodies by investigating plasma small extracellular vesicles enriched for neuronal and microglial origin

  • IRAS ID

    312725

  • Contact name

    Anto Praveen Rajkumar Rajamani

  • Contact email

    Anto.Rajamani@nottingham.ac.uk

  • Sponsor organisation

    University of Nottingham

  • Duration of Study in the UK

    2 years, 11 months, 30 days

  • Research summary

    Background: Dementia with Lewy Bodies (DLB) is the second most common type of dementia, and it causes more disability and challenging behaviours than Alzheimer’s disease (AD). Accurate distinction between DLB and AD is vital because their treatments differ and people with DLB have substantially higher risk of developing life-threatening antipsychotics-related adverse effects. Routine brain scans cannot differentiate DLB from AD accurately. Specialised brain and heart scans that can differentiate DLB from AD are not feasible in most NHS settings. Consequently, nearly 50% people with DLB remain misdiagnosed as AD in UK. There is an urgent need for developing blood-based tests that can be routinely used in clinical settings for improving DLB diagnosis. Genetic material (RNA) in blood reflect disease-related changes in brain. Growing evidence suggest that each type of dementia has a unique blood-based RNA signature. Our preliminary data have confirmed the relationship between brain and blood RNA, and the feasibility of measuring blood-based RNA changes in people with DLB.

    Aims: (i) To identify unique blood-based RNA changes in plasma small extracellular vesicles of people with DLB, (ii) to develop a prototypic blood-based RNA test that can differentiate DLB from AD accurately.

    Methods: We will recruit people with DLB, AD or without dementia (n=60/group; N=180) from two NHS trusts. We will assess severity of clinical symptoms and will collect a venous blood sample from each participant. We will identify unique changes in RNA levels in DLB using next-generation RNA-sequencing. We will verify the RNA-sequencing findings using a targeted RNA assay. We will develop a prototypic blood-based RNA test using our RNA-Sequencing data and a novel Artificial Intelligence based algorithm.

    Expected outcomes: We will identify DLB-associated RNA changes in blood that will set the stage for the development of the first blood-based diagnostic test, suitable for clinical adaption, for DLB.

  • REC name

    North East - Newcastle & North Tyneside 1 Research Ethics Committee

  • REC reference

    22/NE/0160

  • Date of REC Opinion

    21 Oct 2022

  • REC opinion

    Further Information Favourable Opinion