\ua9 2025 Lewy Body Dementia Association and The Author(s). Alzheimer\u27s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer\u27s Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.Dementia with Lewy bodies (DLB), a progressive neurodegenerative disease with heterogeneous clinical presentations, greatly impacts patients, caregivers, and society. Despite its frequency, diagnosing and treating DLB remains challenging. Advances in in vivo biomarker assays reflecting underlying pathology are improving disease identification, diagnostic accuracy, and therapeutic development for biologically targeted, disease-modifying agents. Consequently, definitions of Alzheimer\u27s disease and Parkinson\u27s disease (PD) have shifted to focus on pathological changes occurring before clinical features, with proposed frameworks for detecting pathological amyloid and tau, neurodegeneration, and other markers (National Institute on Aging-Alzheimer\u27s Association) and alpha-synucleinopathy and dopaminergic degeneration (Neuronal α-synuclein Disease Integrated Staging System, SynNeurGe). The biological frameworks, particularly those related to alpha-synuclein (α-synuclein), have sparked debate about unifying DLB and PD under a single pathobiologic disease. This paper discusses the implications of these biological frameworks for the DLB community, addressing topics regarding multiple pathologies and neurochemical systems, clinical heterogeneity, and functional impairment, and exploring the potential impact on clinical trials and care. Highlights: DLB is a progressive neurodegenerative disease with varied clinical presentations. Diagnosing and treating DLB remains challenging despite its frequency. Biological frameworks are reshaping Alzheimer\u27s and Parkinson\u27s definitions. In vivo biomarkers are improving DLB identification and diagnostic accuracy. Debate exists regarding unifying DLB and Parkinson\u27s under one pathobiology
