Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline, memory loss, and behavioural changes. While genetic predispositions and pathological processes have been the traditional focus, this review highlights the fundamental role of environmental factors, particularly nutrition, within the exposome framework in modulating the risk and progression of AD. The exposome, which includes the totality of environmental exposures in an individual's lifetime, provides a comprehensive approach to understanding the complex aetiology of AD. In this review, we explore the impact of dietary factors and cyclic nucleotide pathways (cAMP/cGMP) on AD, emphasizing the potential of dietary interventions as therapeutic strategies. We investigate key aspects of how nutrition affects the accumulation of β-amyloid, the aggregation of tau proteins, and neuroinflammation. We also examine the impact of specific nutrients on cognitive performance and the risk of AD. Additionally, we discuss the potential of nutraceuticals with anti-phosphodiesterase activity and the role of various animal models of AD (such as 5xFAD, 3xTg-AD, Tg2576, and APP/PS1 mice) in demonstrating the effects of dietary interventions on disease onset and progression.
Keywords: Alzheimer’s disease; exposome; microbiota; nutrition; phosphodiesterase (PDE); transgenic mouse models.