Is the Era of One-Size-Fits-All Alzheimer's Treatment Officially Over?

Alzheimer's disease (AD) is prevalent in more than 55 million worldwide, a figure estimated to almost triple by 2050, highlighting the need for highly effective treatments. However, despite the large expenditure of research over several decades, over 90% of clinical trials-countless amyloid-β-targeted drugs among them-have failed, stressing the shortcomings of reductionist, one-target approaches. More and more, AD is viewed as a complex systems disorder, resulting from interlinked disruptions in proteostasis, neuroinflammation, vascular integrity, synaptic plasticity, and metabolic regulation. Such an understanding has transformed the therapeutic paradigm toward precision, multimodal treatment, integrating disease-modifying agents with biomarker-based diagnosis and patient stratification. Improved blood- and imaging-based biomarkers, new molecular targets, and drug-delivery technologies offer the hope for earlier intervention and more personalized treatment. Looking to the future, the way forward will rely on the integration of systems biology, computational modeling, and translational neuroscience into adaptive trial design able to tackle the heterogeneity of the disease. These developments combined constitute the progressive shift away from "one-size-fits-all" treatments towards a future of personalized, mechanism-based therapies in Alzheimer's disease.