The role of precision nutrition, probiotics and prebiotics in ApoE4 carriers as Alzheimer’s disease prevention strategies

Alzheimer’s disease (AD) is the most prominent form of dementia in the USA, with 7·2 million Americans aged 65 years and older, living with AD in 2025. As the US population ages, there is a need for preventative measures to reduce the risk of AD. The apo E ϵ4 (ApoE4) allele is the greatest known genetic risk factor for AD, with heterozygous or homozygous ApoE4 carriers having increased likelihood of developing it. Due to abnormal lipid handling by ApoE4 carriers, precision nutrition may play a major role in delaying the onset of AD in these subjects, with n -3 fatty acids, lipids such as olive oil, vitamins C and E, Mediterranean, ketogenic and high-fibre diets showing promising but still limited evidence for ApoE4 carriers, as most of the current evidence comes from preclinical studies. Additionally, compared with non-carriers, ApoE4 carriers exhibit early gut dysbiosis, an imbalance in the gut microbiota that can disrupt normal digestive, metabolic and immune functions. The potential of probiotics and prebiotics to restore microbial balance and reduce dysbiosis in ApoE4 carriers has also been investigated. This review summarises evidence from observational human cohorts and clinical studies, animal models and in vitro mechanistic studies to examine emerging nutritional and gut-microbiome-based approaches to reduce AD risk in ApoE4 carriers. Future directions include the integration of precision nutrition with multi-omics approaches to allow for scalable and comprehensive analyses of ApoE–diet interactions and utilisation of larger human cohorts to determine the efficacy of nutritional and gut-based AD prevention strategies.