Towards pharmacological prevention of Alzheimer disease.

Prevention of Alzheimer disease (AD) is a medical challenge owing to its complex pathogenesis, which involves amyloid-β (Aβ) and tau aggregation, neuroinflammation and progressive neurodegeneration. Development of disease-specific biomarkers has transformed our ability to detect AD pathology early, enabling more accurate diagnosis, monitoring and the development of targeted disease-modifying therapies. Consequently, primary and secondary prevention of AD have become feasible goals. In this Perspective, we examine current and emerging pharmacological strategies for the prevention of AD, particularly the use of existing anti-Aβ therapies and emerging anti-tau approaches, among people at risk of AD or in the earliest, presymptomatic stages of the disease. We highlight the key challenges in implementing prevention trials, discuss ongoing prevention trials and their implications, and consider the potential and challenges of translation into clinical practice. Implementation of preventative strategies, supported by biomarker-guided patient selection and innovative trial designs, has the potential to substantially delay or prevent the cognitive decline caused by AD. Success would fundamentally transform the AD therapeutic landscape, reducing the socioeconomic burden of dementia and preserving cognitive function in ageing populations worldwide.