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These clinical entities have marked heterogeneity of motor and nonmotor symptoms with highly variable disease progression. The biological basis for this clinical heterogeneity remains poorly understood. Previous attempts to subtype patients within the spectrum of Lewy body disorders have centered on clinical features, but converging evidence from studies of neuropathology and ante mortem biomarkers, including CSF, neuroimaging, and genetic studies, suggest that Alzheimer's disease beta\u2010amyloid and tau copathology strongly influence clinical heterogeneity and prognosis in Lewy body disorders. Here, we review previous clinical biomarker and autopsy studies of Lewy body disorders and propose that Alzheimer's disease copathology is one of several likely pathological contributors to clinical heterogeneity of Lewy body disorders, and that such pathology can be assessed in vivo. Future work integrating harmonized assessments and genetics in PD, PD with dementia, and dementia with Lewy bodies patients followed to autopsy will be critical to further refine the classification of Lewy body disorders into biologically distinct endophenotypes. This approach will help facilitate clinical trial design for both symptomatic and disease\u2010modifying therapies to target more homogenous subsets of Lewy body disorders patients with similar prognosis and underlying biology. \u00a9 2019 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.27867","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T06:50:51Z","timestamp":1572331851000},"page":"5-19","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":114,"title":["Pathological Influences on Clinical Heterogeneity in Lewy Body Diseases"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4111-0102","authenticated-orcid":false,"given":"David G.","family":"Coughlin","sequence":"first","affiliation":[{"name":"Department of Neurology University of Pennsylvania Health System  Philadelphia Pennsylvania USA"},{"name":"Digital 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