Updates in Fluid, Tissue, and Imaging Biomarkers for Dementia with Lewy Bodies and Implications for Biologically Based Disease Definitions

Dementia with Lewy bodies (DLB) remains underrecognized and underdiagnosed due to its clinical and pathological heterogeneity. Diagnosis currently relies on recognition of clinical features and imaging and neurophysiologic biomarkers. However, clinical features are less obvious in mixed neurodegenerative pathologies, advanced imaging techniques are often inaccessible, and current DLB indicative biomarkers do not directly identify Lewy pathology.

Seed amplification assay techniques have allowed for in vivo detection of pathological alpha-synuclein protein in the cerebrospinal fluid, blood, and dermal biosamples. Incorporation of co-pathology markers and refinement of the application and interpretation of existing tests for DLB, including brain and cardiac imaging, are also ongoing. Strategic combinations of Lewy biomarkers with other markers of neurodegeneration and neuroinflammation could create individualized patient profiles for diagnosis, prognosis, treatment selection, and response monitoring.

Continued validation and technical harmonization efforts will be needed prior to widespread clinical application of new Lewy body biomarkers. Combining existing and novel DLB and co-pathology biomarkers, along with thorough clinical evaluation, will lead to increased reliability and accuracy of etiological dementia diagnosis. Use of biomarker profiles and biologically based disease definitions will improve care and accelerate treatment discovery for people living with DLB.