F Licastro

..This information may better define the pathogenesis of myocardial infarction and identify individuals who might benefit from early interventions...

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..Our findings suggest that IL-1beta gene by affecting brain immune responses may influence the age at onset of the disease, survival and AD progression...

..The administration of anti-inflammatory compounds to middle age healthy subjects with increased genetic susceptibility of developing MI might decrease the incidence and prevalence of cardiovascular events in aging...

..An altered regulation of these molecules might interfere with some processes involved in cognitive performances of DS subjects...

..Recent studies have shown that many inflammatory genes are associated with the risk of PCa. Alpha 1 antichymotrypsin (ACT) is an acute phase protein and it is part of the circulating prostate specific antigen (PSA)...

..Altered intestinal absorption of nutrients may in turn affect endocrine functions, brain development, and cognitive performances...

..The ACT gene appears to influence the early clinical development of the disease, and the interaction of the ACT and APOE genes affects clinical progression of AD...

..Peripheral altered immune phenotype in healthy young subjects with DS might be an early sign of CNS alterations leading many years later to cognitive deterioration and dementia...

..Detection of these molecules might be used for monitoring the progression of brain inflammation associated with AD...

..The gender effect appeared to be prominent, since female AD patients with APOE 3,3 had similar ACT levels to those of female AD patients with APOE 4,4...

..This data analysis method was compared with another mathematical model called mutual information relevance network and results are presented and discussed...

..Present findings indicated that subjects with ACT TT genotype had an increased risk of developing AD and suggested that this genotype influenced the risk of an early onset of the disease by affecting the production of ACT molecules...

..Elevated ACT levels in the brain of AD patients could be interpreted as a metabolic response of astrocytes which might modulate the potentially deleterious activation of microglia cells...

..Both the -174 CC and VNTR DD genotypes were also associated with increased IL-6 levels in the blood and brain from AD. These findings suggest that IL-6 may play a multifaceted role in AD by affecting the turnover of the cytokine...

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..The development of compounds able to interfere with the ACT biological activity (protease inhibition and/or promotion of amyloid deposition) might have therapeutic relevance for the disease...

..Our data suggest that different genetic background in the Fas gene may influence the risk and clinical progression of the disease by affecting neurodegenerative processes leading to neuronal loss...

..ACT might be implicated in controlling oxidative damage of blood lipids and their turnover during the progression of AD...

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..We integrated this information to better define risk and determine the relative importance of APOE and immunological mediators...

..Our findings suggest that the G51S PNP polymorphism is associated with a faster rate of cognitive decline in AD patients, highlighting the important role of purine metabolism in the progression of this neurodegenerative disorder...

..Present findings reinforce the notion that abnormal regulation of cholesterol metabolism is a key factor in the pathogenesis of the disease...

..The possibility as well as the difficulty in identifying a pro-inflammatory phenotype, and its importance for the prevention, diagnosis and therapy of AD and other age-related pathologies are discussed...

..An overload of dietary antigens and impaired nutrient absorption secondary to altered functioning of the gastrointestinal mucosa might interfere with normal immune responses by inducing programmed cell death in CD4 T-cells...

..The endocrine function of the thymus of patients with dementia appears to be more compromised than that from aged controls...

..This is relevant to Alzheimer's disease because these two molecules appear to be closely associated with the pathogenesis of this disorder...

..Up-regulation of vascular andothelial growth factor (VEGF)-mediated signals and increased nerve growth factor (NGF) expression might be two of these important protective factors...

..Differential therapeutic actions of these drugs may be advantageously used in clinical practice and further improve the great potential of individual TNF-alpha inhibitors...

..31, 95%CI: 0.13-0.76]. In conclusion, although associated with increased sIL6 levels in presence of major diseases, the IL6-174 C-allele does not seem to have direct detrimental effects on survival in older age...

..The associations of endogenous sex hormones with risk of dementia in the elderly population are not well known...

..The relationship between the AD risk factor plasma tHcy and the IL-1beta-511 polymorphism was never reported before and might explain previous cross-sectional reports of an association between this polymorphism and AD...

..Homocysteine, another risk factor for vascular disease and dementia, also binds to VLDL in blood. However, the association between APOE4 and hyperhomocysteinemia has never been thoroughly investigated...

..91; 95%CI, 1.02-3.56) but not VaD risk. Blood inflammatory markers are associated with increased VaD risk but do not predict AD, which seems selectively associated with hyperhomocysteinemia...

..In addition, the authors investigated whether patterns of association also were found for mild cognitive impairment (MCI) and conversion from MCI to AD...

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..CONCLUSION : This map of variables may be use to identify subjects with increased risk of developing cognitive decline end/or dementia and provide pivotal information for early intervention protocols for prevention of dementia...

..It is unclear whether high levels of blood inflammatory proteins are associated with the risk of developing depression in late life...

..abstract:..

..In fact, predictive diagnostics, personalized medicine and personalized therapy have the potential of changing classical approaches of modern medicine to CDD...

..In cross-sectional studies, elevated plasma total homocysteine (tHcy) concentrations have been associated with cognitive impairment and dementia. Incidence studies of this issue are few and have produced conflicting results...

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..Our results indicate that this group of "healthy old" Down syndrome patients, although showing some classical biochemical risk factors for atherosclerosis, did not suffer clinical cardiovascular alterations...

..Only this group of patients may benefit from anti-inflammatory treatment...

..The GNMT T allele may influence PCa risk by affecting DNA methylation and prostate gene expression. Our observations might help implement the screening of unaffected subjects with an increased susceptibility to develop PCa...

..All together this information may represent the basis both for future recognition of individuals at risk as well as for a pharmacogenomic approach in achieving drug responsiveness...

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..However, it has to be taken into account that there are many molecular HLA-A2 subtypes with different frequencies in various populations. Therefore, further studies should include molecular typing of HLA-A2 subtypes...

..To our knowledge, no data have yet been presented on the association between AD and polymorphisms of the interferon(IFN)-gamma gene, despite the pivotal role that IFN-gamma plays in immune-mediated inflammatory responses...

..All together this information may represent the basis both for future recognition of individuals at risk and for the pharmacogenomic driving of drug responsiveness...

..Down's syndrome (DS) is the most frequent chromosomal aberration in men and it is invariably associated with mental retardation...

..Thus, our study, performed in two samples of genetically homogeneous patients and controls, does not support the suggestion that HFE mutations may be associated with acute myocardial infarction in susceptible individuals...

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..Thus, our study does not support the suggestion that H63D mutations may anticipate sporadic AD clinical presentation in susceptible individuals...

..Further, studies should focus on identification of proinflammatory genetic variants involved in AD pathogenesis in women...

..These data suggest that (1) IL6 exerts protective functions by upregulating the expression of aFGF and (2) the IL6/IL1beta balance in the brain may regulate neuronal survival during neuropathological processes...

..The relevance on the cholesterol metabolism in Alzheimer's disease pathogenesis is also discussed...

..These outcomes can be related to the additional program of home attendance. The correlation between pro-inflammatory cytokine levels and degree of frailty are observed in both groups without statistically significant difference...