Physical Exercise and Alzheimer’s Disease: Effects on Pathophysiological Molecular Pathways of the Disease (original) (raw)
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The Systemic Effects of Exercise on the Systemic Effects of Alzheimer’s Disease
Antioxidants
Alzheimer’s disease (AD) is a progressive degenerative disorder and a leading cause of dementia in the elderly. The etiology of AD is multifactorial, including an increased oxidative state, deposition of amyloid plaques, and neurofibrillary tangles of the tau protein. The formation of amyloid plaques is considered one of the first signs of the illness, but only in the central nervous system (CNS). Interestingly, results indicate that AD is not just localized in the brain but is also found in organs distant from the brain, such as the cardiovascular system, gut microbiome, liver, testes, and kidney. These observations make AD a complex systemic disorder. Still, no effective medications have been found, but regular physical activity has been considered to have a positive impact on this challenging disease. While several articles have been published on the benefits of physical activity on AD development in the CNS, its peripheral effects have not been discussed in detail. The provocati...
Exercise plays a preventive role against Alzheimer's disease
Journal of Alzheimer's disease : JAD, 2010
Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting the elderly population. It is predicted that the incidence of AD will be increased in the future making this disease one of the greatest medical, social, and economic challenges for individuals, families, and the health care system worldwide. The etiology of AD is multifactorial. It features increased oxidative state and deposition of amyloid plaques and neurofibrillary tangles of protein tau in the central cortex and limbic system of the brain. Here we provide an overview of the positive impacts of exercise on this challenging disease. Regular physical activity increases the endurance of cells and tissues to oxidative stress, vascularization, energy metabolism, and neurotrophin synthesis, all important in neurogenesis, memory improvement, and brain plasticity. Although extensive studies are required to understand the mechanism, it is clear that physical exercise is beneficial in the prevention of AD ...
Current Alzheimer Research, 2012
Physical activity has been correlated with a reduced incidence of cognitive decline and Alzheimer's disease in human populations. Although data from intervention-based randomized trials is scarce, there is some indication that exercise may confer protection against age-related deficits in cognitive function. Data from animal models suggests that exercise, in the form of voluntary wheel running, is associated with reduced amyloid deposition and enhanced clearance of amyloid beta, the major constituent of plaques in Alzheimer's disease. Treadmill exercise has also been shown to ameliorate the accumulation of phosphorylated tau, an essential component of neurofibrillary tangles in Alzheimer's models. A common therapeutic theme arising from studies of exercise-induced neuroprotection in human populations and in animal models involves reduced inflammation in the central nervous system. In this respect, physical activity may promote neuronal resilience by reducing inflammation.
Physical Activity and Alzheimer Disease: A Protective Association
Mayo Clinic Proceedings, 2016
Financial support: Research in the field by A. Lucia is supported by grants from the Spanish Ministry of Economy and Competitiveness [Fondo de Investigaciones Sanitarias (FIS), grant number PI12/00914] and cofinanced by Fondos Feder. Fiuza-Luces C. is supported through the postdoctoral Sara Borrell contract (file number CD14/00005) by the Institute of Health Carlos III (ISCIII), the main Public Research Entity funding, managing and carrying out biomedical research in Spain. The ISCIII reports directly to the Ministry of Economy and Competitiveness and in operational terms to both this Ministry and to the Ministry of Health, Social Services and Equality.
Experimental Gerontology, 2019
Background: Neuroinflammation is recognized as part of the pathological progression of Alzheimer's disease (AD), but the molecular mechanisms are still not entirely clear. Systemically, physical exercise has shown to have a positive modulating effect on markers of inflammation. It is not known if this general effect also takes place in the central nervous system in AD. The aim of this study was to investigate the effect of 16 weeks of moderate to high-intensity physical exercise on selected biomarkers of inflammation both systemically and in the CNS, in patients with AD. Methods: Plasma and cerebrospinal fluid (CSF) from 198 patients with Alzheimer's disease participating in the Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX) study were analyzed for concentrations of 8-isoprostane, soluble trigger receptor expressed on myeloid cells 2 (sTREM2), and the MSD v-plex proinflammation panel 1 human containing interferon gamma (IFNγ), Interleukin-10 (IL10), IL12p70, IL13, IL1β, IL2, IL4, IL6, IL8, and tumor necrosis factor alpha (TNFα), before and after a 16-week intervention with physical exercise, and we studied whether changes were modulated by the patients' APOE genotype. Results: Most inflammatory markers remained unchanged after exercise. We found an increasing effect of 16 weeks of physical exercise on sTREM2 measured in CSF. Further, IL6 in plasma increased in the exercise group after physical exercise (mean relative change 41.03, SD 76.7), compared to controls (−0.97, SD 49.4). In a sub-analysis according to APOE genotype, we found that in ε4 carriers, exercise had a stabilizing effect on IFNγ concentration with a mean relative change of 7.84 (SD 42.6), as compared to controls (114.7 (SD 188.3), p = 0.038. Conclusion: Our findings indicate an effect of physical exercise on markers of neuroinflammation in CSF measured by an increase in sTREM2 in patients with AD. Further, there may be a small inflammatory systemic effect related to physical exercise in patients with AD.
Protective effects of different exercise modalities in an Alzheimer’s disease-like model
Behavioural Brain Research, 2017
Highlights► Aerobic exercise improves anxiety-like behaviour in an Alzheimer's disease-like model. ► Aerobic, resistance and combined exercises protect from oxidative stress and memory decline. ► Exercise has neurotrophic effects. ► Exercise decreases Aβ burden in developmental stage of Alzheimer's disease-like conditions. Abstract Our aim was to investigate the probable protective effects of aerobic, resistance and combined exercise methods on ovariectomy and D-galactose induced Alzheimer's Disease (AD)-like model. D-galactose (100 mg/kg) or saline were administered intraperitoneally for 6 weeks to ovariectomized or sham-operated rats (n=8/group). Aerobic (AE), resistance (RE) and combined exercises (CE) (aerobic+resistance) were performed for 3 times a week for 6 weeks. Anxiety level and cognitive functions were evaluated via hole-board and object recognition tests. Brain myeloperoxidase, malondialdehyde, nitric oxide activity, lucigeninenhanced chemiluminescence, glutathione and serum insulin like growth factor-I (IGF-I) assays were done. Hippocampal mRNA levels of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and amyloid precursor protein 695 (APP695) were measured. Amyloid Beta (Aβ), NGF, BDNF, IGF-I immunoreactive neurons were evaluated. Freezing time were increased in AD-like model and decreased back with AE (p<0.05). Deteriorated working memory in AD-like model was improved with all exercise types (p<0.05-0.001). Reduced glutathione levels in AD-like model were increased and increased malondialdehyde levels were reduced and serum IGF-I levels were increased by all exercises (p<0.05-0.001). Increased APP mRNA levels in AD-like model were decreased via CE (p<0.05). Elevated Aβ scores in AD-like model were decreased by RE and CE (p<0.01) in hippocampus and by all exercise types in cortex (p<0.05-0.01). Decreased cortical NGF immunocytochemical scores of AD-like model were increased by CE (p<0.05). Different exercise models may have
Journal of Neuroinflammation, 2008
Background: Inflammation is associated with Aβ pathology in Alzheimer's disease (AD) and transgenic AD models. Previously, it has been demonstrated that chronic stimulation of the immune response induces pro-inflammatory cytokines IL-1β and TNF-α which contribute to neurodegeneration. However, recent evidence has shown that inducing the adaptive immune response reduces Aβ pathology and is neuroprotective. Low concentrations of IFN-γ modulate the adaptive immune response by directing microglia to differentiate to antigen presenting cells. Our objective was to determine if exercise could induce a shift from the immune profile in aged (17-19 months) Tg2576 mice to a response that reduces Aβ pathology. Methods: TG (n = 29) and WT (n = 27) mice were divided into sedentary (SED) and exercised (RUN) groups. RUN animals were provided an in-cage running wheel for 3 weeks. Tissue was harvested and hippocampus and cortex dissected out. Quantitative data was analyzed using 2 × 2 ANOVA and student's t-tests. Results: IL-1β and TNF-α were significantly greater in hippocampi from sedentary Tg2576 (TG SED) mice than in wildtype (WT SED) (p = 0.04, p = 0.006). Immune response proteins IFN-γ and MIP-1α are lower in TG SED mice than in WT SED (p = 0.03, p = 0.07). Following three weeks of voluntary wheel running, IL-1β and TNF-α decreased to levels indistinguishable from WT. Concurrently, IFNγ and MIP-1α increased in TG RUN. Increased CD40 and MHCII, markers of antigen presentation, were observed in TG RUN animals compared to TG SED , as well as CD11c staining in and around plaques and vasculature. Additional vascular reactivity observed in TG RUN is consistent with an alternative activation immune pathway, involving perivascular macrophages. Significant decreases in soluble Aβ 40 (p = 0.01) and soluble fibrillar Aβ (p = 0.01) were observed in the exercised transgenic animals. Conclusion: Exercise shifts the immune response from innate to an adaptive or alternative response. This shift in immune response coincides with a decrease in Aβ in advanced pathological states.
Physical exercise protects against Alzheimer's disease in 3xTg-AD mice
Journal of Alzheimer's disease : JAD, 2011
Physical exercise is considered to exert a positive neurophysiological effect that helps to maintain normal brain activity in the elderly. Expectations that it could help to fight Alzheimer's disease (AD) were recently raised. This study analyzed the effects of different patterns of physical exercise on the 3xTg-AD mouse. Male and female 3xTg-AD mice at an early pathological stage (4-month-old) have had free access to a running wheel for 1 month, whereas mice at a moderate pathological stage(7-month-old) have had access either during 1 or 6 months. The non-transgenic mouse strain was used as a control. Parallel animal groups were housed in conventional conditions. Cognitive loss and behavioral and psychological symptoms of dementia (BPSD)-like behaviors were present in the 3xTg-AD mice along with alteration in synaptic function and ong-term potentiation impairment in vivo. Brain tissue showed AD-pathology and oxidative-related changes. Disturbances were more severe at the older ...
Physical Activity and Alzheimer’s Disease: A Narrative Review
Aging and disease
Although age is a dominant risk factor for Alzheimer's disease (AD), epidemiological studies have shown that physical activity may significantly decrease age-related risks for AD, and indeed mitigate the impact in existing diagnosis. The aim of this study was to perform a narrative review on the preventative, and mitigating, effects of physical activity on AD onset, including genetic factors, mechanism of action and physical activity typology. In this article, we conducted a narrative review of the influence physical activity and exercise have on AD, utilising key terms related to AD, physical activity, mechanism and prevention, searching the online databases; Web of Science, PubMed and Google Scholar, and, subsequently, discuss possible mechanisms of this action. On the basis of this review, it is evident that physical activity and exercise may be incorporated in AD, notwithstanding, a greater number of high-quality randomised controlled trials are needed, moreover, physical activity typology must be acutely considered, primarily due to a dearth of research on the efficacy of physical activity types other than aerobic.
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2015
Physical exercise is suggested for preventing or delaying senescence and Alzheimer's disease (AD). We have examined its therapeutic value in the advanced stage of AD-like pathology in 3xTg-AD female mice through voluntary wheel running from 12 to 15 months of age. Mice submitted to exercise showed improved body fitness, immunorejuvenation, improvement of behavior and cognition, and reduced amyloid and tau pathology. Brain tissue analysis of aged 3xTg-AD mice showed high levels of oxidative damage. However, this damage was decreased by physical exercise through regulation of redox homeostasis. Network analyses showed that oxidative stress was a central event, which correlated with AD-like pathology and the AD-related behaviors of anxiety, apathy, and cognitive loss. This study corroborates the importance of redox mechanisms in the neuroprotective effect of physical exercise, and supports the theory of the crucial role of oxidative stress in the switch from normal brain aging to pathological aging and AD.