Alzheimer's disease heterogeneity and co‐pathologies: Defining novel targets, biomarkers, modalities, and research methodologies

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Alzheimer's disease (AD) is a biologically heterogeneous condition with vascular, proteinopathic, metabolic, and immune processes jointly shaping its clinical expression, trajectory of progression, and response to therapeutic intervention. Common AD co‐pathologies such as cerebral amyloid angiopathy, Lewy body pathology, α‐synuclein, and transactive response DNA‐binding protein of 43 kDa (TDP‐43)/limbic‐predominant age‐related TDP‐43 encephalopathy are also increasingly connected with cognitive decline and therapeutic response. Significant advances in biomarkers, including seed amplification assays, proteomic signatures, and emerging positron emission tomography tracers bolster the field's understanding of a biological staging model and discovery of previously unrecognized co‐pathologies. The Fall 2025 Alzheimer's Association Research Roundtable (AARR) brought together academic, clinical, and industry leaders to discuss and explore the current advances in the heterogeneity and co‐pathologies of AD, and their implications for diagnosis, clinical trial design, and precision treatment strategies. This paper presents key takeaways from the Fall 2025 AARR meeting.