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Neuropathologically, it is characterized by the presence of Lewy pathology. However, neuropathological studies have demonstrated the high prevalence of coexistent Alzheimer's disease, TAR DNA\u2010binding protein 43 (TDP\u201043), and cerebrovascular pathologic cases. Due to their high prevalence and clinical impact on DLB individuals, clinical trials should account for these co\u2010pathologies in their design and selection and the interpretation of biomarkers values and outcomes. Here we discuss the frequency of the different co\u2010pathologies in DLB and their cross\u2010sectional and longitudinal clinical impact. We then evaluate the utility and possible applications of disease\u2010specific and disease\u2010nonspecific biomarkers and how co\u2010pathologies can impact these biomarkers. 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