10091160BBDLB: A novel multiplex plasma extracellular vesicle RNA biomarker assay for improving clinical diagnosis of Dementia with Lewy BodiesClosedCollaborative R&DInnovate UK**Clinical need:** Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the two most common types of progressive dementia. Routine brain scans cannot differentiate them. Highly specialised brain and heart scans that can differentiate DLB from AD are not feasible in most NHS mental health settings. Consequently, nearly 50% people with DLB may remain misdiagnosed as AD in UK. Distinguishing DLB from AD accurately is important because their treatments differ. People with DLB have substantially higher risk for antipsychotics-related adverse effects. Missing DLB diagnosis, and prescribing an antipsychotic for managing hallucinations and/or challenging behaviours that are more frequent in DLB than AD may cause life-threatening adverse events. Currently, there is no blood or cerebrospinal fluid based diagnostic biomarker for DLB. There is an urgent need for developing a blood-based test that can be routinely used in clinical settings for differentiating DLB from AD accurately. **Proposed solution**: Brain cells release tiny(30-100nm) particles that transport genetic material (RNA) between brain and blood. These nanoparticles make measuring disease-related changes in brain by testing blood samples possible. Growing evidence indicate that DLB and AD differ on their brain inflammatory responses. Overactive brain immune cells and heightened inflammatory response contribute to AD progression. However, several lines of evidence have demonstrated that such overactive inflammatory response is absent in DLB. Our prior research have confirmed reduced levels of a list of inflammation-related RNA in both post-mortem DLB brains and blood-based nanoparticles from people living with DLB. We aim to develop a blood-based inflammation-focused RNA test (**BBDLB**) and to evaluate its diagnostic accuracy. **Project**: We will design the BBDLB assay using our list of inflammation-related RNA and a cutting-edge RNA measurement (_NanoString miRGE_) technology. We have obtained necessary ethics approval, and will collect blood samples from people with DLB, AD or without dementia (30people/group) from three NHS trusts. We will extract RNA from blood samples, and will evaluate diagnostic accuracy of the BBDLB assay for distinguishing DLB from AD and from those without dementia. **PPI**: Our ongoing consultation activities with the Nottingham University Hospitals PPI and Engagement group, and the Nottinghamshire Dementia Action Alliance will support all aspects of this project. **Impact**: This will accelerate development of the first blood-based test that can be adapted for routine use in the UK NHS memory assessment services for differentiating DLB from AD. Improving accurate diagnosis of DLB will help minimising antipsychotic prescriptions and planning safer multidisciplinary clinical care.