Abstract
Alzheimer’s disease (AD), the most common form of neurodegenerative dementia in adults worldwide, is a multifactorial and heterogeneous disorder characterized by the interaction of genetic and epigenetic factors and the dysregulation of numerous intracellular signaling and cellular/molecular pathways. The introduction of the systems biology framework is revolutionizing the study of complex diseases by allowing the identification and integration of cellular/molecular pathways and networks of interaction. Here, we reviewed the relationship between physical activity and the next pathophysiological processes involved in the risk of developing AD, based on some crucial molecular pathways and biological process dysregulated in AD: (1) Immune system and inflammation; (2) Endothelial function and cerebrovascular insufficiency; (3) Apoptosis and cell death; (4) Intercellular communication; (5) Metabolism, oxidative stress and neurotoxicity; (6) DNA damage and repair; (7) Cytoskeleton and membrane proteins; (8) Synaptic plasticity. Moreover, we highlighted the increasingly relevant role played by advanced neuroimaging technologies, including structural/functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labelling, in exploring the link between AD and physical exercise. Regular physical exercise seems to have a protective effect against AD by inhibiting different pathophysiological molecular pathways implicated in AD.
Highlights
Physical Activity and Alzheimer’s DiseaseLife expectancy is increasing steadily worldwide [1], and this population trend has been associated with an increase in the incidence of chronic diseases [2,3]
This review summarizes the effect of physical activity (PA) on the different pathophysiological molecular pathways characterizing Alzheimer’s disease (AD), assessed through the systems biology framework
Plasma concentrations of metabolites from both cholinergic and serotonergic pathways have been found to be altered in mild cognitive impairment (MCI) due to AD (MCI-AD) participants compared to healthy control individuals and linked to cognitive impairment and neurodegeneration
Summary
Life expectancy is increasing steadily worldwide [1], and this population trend has been associated with an increase in the incidence of chronic diseases [2,3]. More than 50 genes/loci associated with the risk of developing LOAD have been disclosed so far via large-scale genomics studies, including genome-wide association studies (GWAS), meta-analyses of GWAS, and next-generation sequencing (NGS)-based analyses [30,31,32] These approaches facilitated the investigation of disease pathomechanisms potentially involved in AD etiology. The following primary pathophysiological molecular pathways were identified by two independent authors (SLO and ASL) after the literature search for relevant articles (Figure 1, all images have been created using BioRender software [45]): (I) immune system and inflammation, (II) endothelial function and cerebrovascular insufficiency, (III) apoptosis and cell death, (IV) intercellular communication, (V) metabolism, oxidative stress and neurotoxicity, (VI) DNA damage and repair, (VII) cytoskeleton and membrane proteins, and (VIII) synaptic plasticity
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