The Impact of the Exposome on Alzheimer's Disease: The Influence of Nutrition

Abstract

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.

Figure 1

The figure illustrates the common workflow to characterize dietary biomarkers.

Figure 2

The figure illustrates the comparison between a healthy brain and an atrophic brain associated with AD. It highlights environmental and lifestyle factors influencing brain health, including a healthy diet and supplements as protective measures, versus air pollution and high-fat diets as risk factors for developing AD. Key pathological mechanisms linked to the exposome are shown, including neuroinflammation, gut–brain axis disruption, Aβ deposition, oxidative stress, and altered cAMP/cGMP pathways. The figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license (https://smart.servier.com/, accessed on 21 January 2025).