From protein biomarkers to proteomics in dementia with Lewy Bodies

Dementia with Lewy Bodies (DLB) is the second most common neurodegenerative dementia. Despite consider-able research progress, there remain gaps in our understanding of the pathophysiology and there is no disease-modifying treatment. Proteomics is a powerful tool to elucidate complex biological pathways across heteroge-nous conditions. This review summarizes the widely used proteomic methods and presents evidence for protein dysregulation in the brain and peripheral tissues in DLB. Proteomics of post-mortem brain tissue shows that DLB shares common features with other dementias, such as synaptic dysfunction, but retains a unique protein signature. Promising diagnostic biomarkers are being identified in cerebrospinal fluid (CSF), blood, and pe-ripheral tissues, such as serum Heart-type fatty acid binding protein. Research is needed to track these changes from the prodromal stage to established dementia, with standardized workflows to ensure replicability. Identi-fying novel protein targets in causative biological pathways could lead to the development of new targeted therapeutics or the stratification of participants for clinical trials.