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Fig. 3 | Molecular Neurodegeneration

Fig. 3

From: ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies

Fig. 3

Lifestyle changes can influence the pathogenesis of AD. ApoE4 has been shown to increase Aβ and tau aggregation, inflammation, and lipid dysregulation while reducing glucose metabolism, microbiome diversity, and BBB integrity. Healthy lifestyle changes have been suggested to benefit cognitive function and ameliorate AD pathology even in the presence of APOE4. Studies have demonstrated that ketogenic and Mediterranean diets as well as dietary supplements such as DHA can improve clinical outcomes. Along with diet, exercise has been shown to improve AD prognosis in apoE4 carriers. Chronic sleep disturbance appears to accelerate Aβ and tau pathology and exacerbate cognitive symptoms. The influence of APOE4 on sleep quality may lead to sleep disturbances in people at increased risk for dementia. Thus, improving sleep quality could reduce AD pathology and attenuate the negative impact of APOE4 on AD risk. The communication between gut microbiome and the brain, the microbiota-gut-brain axis, plays an important role in modulating AD pathology. ApoE isoforms have been shown to differentially modulate microbiome diversity. Evidence supports the use of sesamol to reshape the gut microbiome and prevent systemic inflammation. Thus, understanding the link between AD, apoE, and gut microbiota modulated through dietary approaches may offer avenues for identifying novel biomarkers and therapeutic strategies against AD

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