Article

Stress, exercise, and Alzheimer's disease: A neurovascular pathway

University of California San Diego, School of Medicine, Department of Psychiatry, San Diego, CA, USA.
Medical Hypotheses (Impact Factor: 1.07). 03/2011; 76(6):847-54. DOI: 10.1016/j.mehy.2011.02.034
Source: PubMed

ABSTRACT Genetic factors are known to play a role in Alzheimer's disease (AD) vulnerability, yet less than 1% of incident AD cases are directly linked to genetic causes, suggesting that environmental variables likely play a role in the majority of cases. Several recent human and animal studies have examined the effects of behavioral factors, specifically psychological stress and exercise, on AD vulnerability. Numerous animal studies have found that, while stress exacerbates neuropathological changes associated with AD, exercise reduces these changes. Some human studies suggest that psychological stress can increase the risk of developing AD, while other studies suggest that exercise can significantly reduce AD risk. Most animal studies investigating the mechanisms responsible for the effects of these behavioral factors have focused on neuronal processes, including the effects of stress hormones and neurotrophic factors on the neuropathological hallmarks of AD, namely amyloid-beta (Aβ) deposition and tau-phosphorylation. However, cumulative evidence indicates that, in humans, AD is associated with the presence of cerebrovascular disease, and cardiovascular risk factors are associated with increased risk of developing AD. There is an extensive literature demonstrating that behavioral factors, particularly stress and exercise, can powerfully modulate the pathophysiology of vascular disease. Thus, the following model proposes that the influence of stress and exercise on AD risk may be partially due to the effects of these behavioral factors on vascular homeostasis and pathology. These effects are likely due to both indirect modification of AD risk through alterations in vascular risk factors, such as hypertension, diabetes, and aortic stiffening, as well as direct influence on the cerebrovasculature, including changes in cerebral blood flow, angiogenesis, and vascular disease. Future studies examining the effects of behavioral factors on AD risk should incorporate measures of both peripheral and cerebral vascular function to further our understanding of the mechanisms by which behavior can modify AD susceptibility. Greater knowledge of the molecular mechanisms behind these behavioral effects would further our understanding of the disease and lead to innovative treatment and preventive approaches.

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    • "We collected all the genes from GeneCards,[13] integrated, database of human genes that provides concise genomic related information, on all known and predicted human genes. By literature survey it is reported that Alzheimer patients have a high risk of having obesity,[14] cholesterolemia,[15] Diabetes type 2[16] and hypertension.[17] There are some biochemical marker which is reported in research papers. "
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    ABSTRACT: Alzheimer Disease (AD) is an outcome as well as source of many diseases. Alzheimer is linked with many other diseases like Diabetes type 2, cholesterolemia, hypertension and many more. But how each of these diseases affecting other is still unknown to scientific community. Signaling Pathways of one disease is interlinked with other disease. But to what extent healthy brain is affected when any signaling in human body is disturbed is the question that matters. There is a need of Pathway analysis, Protein-Protein interaction (PPI) and the conserved interactome study in AD and linked diseases. It will be helpful in finding the potent drug or vaccine target in conscious manner. In the present research the Protein-Protein interaction of all the proteins involved in Alzheimer Disease is analyzed using ViSANT and osprey tools and pathway analysis further reveals the significant genes/proteins linking AD with other diseases.
    Annals of Indian Academy of Neurology 03/2014; 17(1):48-54. DOI:10.4103/0972-2327.128551 · 0.51 Impact Factor
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    • "This may predispose the anterior hippocampus to exhibit the most volume loss when HPA function is disrupted. Dysregulation of such neuroendocrine function has long been linked with advancing age [57] [58] [59], and has also been implicated in other disorders such as AD [60] [61], clinical depression [62], and chronic stress [63]. Coupled with knowledge about hippocampal projections to surrounding tissue, examining the subdivisions of the hippocampus may provide a richer understanding of these conditions. "
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    ABSTRACT: The hippocampus is often treated as a uniform structure, but possesses differential projections to surrounding cortex along its longitudinal axis. This heterogeneity could create varied susceptibility to pathological influences, potentially leading to non-uniform volumetric associations with advancing age and Alzheimer's disease (AD). Previous examinations of aging and AD effects on hippocampal subdivisions have produced highly discrepant findings. To clarify these inconsistencies, we examined the hippocampal head, body, and tail in a large sample of 292 cognitively normal, 37 very mildly demented, and 18 mildly demented individuals, divided into two independent samples. As often done in the literature, we characterized qualitative patterns across these regions, but extended these results by explicitly testing for quantitative differences. In each sample of cognitively normal individuals, the head and body demonstrated greater age effects than the tail. In each sample contrasting AD and cognitively normal individuals, all three regions showed significant volume reductions, with the greatest effect on the head. When examining increasing severity of dementia, the hippocampal head showed progressive volume loss, while the body and tail did not. The patterns of results examining both aging and AD were relatively consistent across the independent samples. These results indicate that there is an anterior-to-posterior gradient of loss within the hippocampus with both advancing age and AD.
    Journal of Alzheimer's disease: JAD 06/2013; 37(1). DOI:10.3233/JAD-130011 · 4.15 Impact Factor
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    • "Some studies on transgenic mouse models of AD have showed beneficial effects of exercise on general activity, spontaneous alternation, object recognition memory[15] and, spatial learning performance.[1617] Some animal studies have revealed that treadmill running improves spatial and passive avoidance learning in NBM-lesion rats.[418] "
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    ABSTRACT: Alzheimer's disease was known as a progressive neurodegenerative disorder in the elderly and is characterized by dementia and severe neuronal loss in the some regions of brain such as nucleus basalis magnocellularis. It plays an important role in the brain functions such as learning and memory. Loss of cholinergic neurons of nucleus basalis magnocellularis by ibotenic acid can commonly be regarded as a suitable model of Alzheimer's disease. Previous studies reported that exercise training may slow down the onset and progression of memory deficit in neurodegenerative disorders. This research investigates the effects of treadmill running on acquisition and retention time of passive avoidance deficits induced by ibotenic acid nucleus basalis magnocellularis lesion. MALE WISTAR RATS WERE RANDOMLY SELECTED AND DIVIDED INTO FIVE GROUPS AS FOLLOWS: Control, sham, Alzheimer, exercise before Alzheimer, and exercise groups. Treadmill running had a 21 day period and Alzheimer was induced by 5 μg/μl bilateral injection of ibotenic acid in nucleus basalis magnocellularis. Our results showed that ibotenic acid lesions significantly impaired passive avoidance acquisition (P < 0.01) and retention (P < 0.001) performance, while treadmill running exercise significantly (P < 0.001) improved passive avoidance learning in NBM-lesion rats. Treadmill running has a potential role in the prevention of learning and memory impairments in NBM-lesion rats.
    International journal of preventive medicine 02/2013; 4(2):187-92.
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