16 alzheimer s disease approaches to pathogenesis in the genomic age

... with Alzheimer' s disease was low and declining according to the severity of the disease therefore it was needed to assess and monitor patients' quality of life during the treatment process and to ... indicated by memory loss, the most characteristic symptoms of disease and other cognitive disorders such as Aphasia, apraxia, agnosia, lost the ability to synthesize reasoning and dysfunction implementation, ... disorders This situation was similar to the clinical literature review in Alzheimer' s disease and in other countries 4.1.1.3 Quality of life of people with Alzheimer' s disease Assessing the quality...

Ngày tải lên: 25/07/2014, 11:36

... ES cell, the underlying mechanisms remain obscure Using the ES fusion system, Smith has found an unexpected role for the homeodomain-containing protein Nanog in this process By boosting levels ... investigating the question of how ES cells commit to the neural lineage He turned this question on its head by asking how somatic cells such as neural stem cells can become reprogrammed to a ... derive rat ES cells Shinohara hinted that he was making progress in applying his findings to the rat Finally, Tariq Enver (University of Oxford, UK) described a mathematical model, developed in collaboration...

Ngày tải lên: 14/08/2014, 16:21

... findings in the aged wolverine and polar bear resemble AD more closely than in most species examined to date, their inaccessibility to laboratory researchers limits the usefulness of these species ... which inhibit different steps in the complement cascade All of these regulatory proteins are produced in the human brain, but less is known about their CNS synthesis in other species [31] The status ... carries both of these transgenes and has been extensively used as a model for studying processes relating to the formation of SPs Aβ deposition occurs more rapidly in these mice than in the single...

Ngày tải lên: 19/06/2014, 22:20

... box plots The box represents the interquartile range that contains 50% of the values The whiskers extend from the box to the highest and lowest values The line across the box indicates the median ... Increased neuronal COX-2 expression leads to increased expression of cell cycle mediators in post mitotic neurons, as shown using a transgenic mouse model with increased neuronal COX-2 expression ... mechanisms involved in the response to intraneuronal accumulation of Aβ and the consequent impaired synaptic function needs to be addressed in future studies Competing interests The author (s) declare...

Ngày tải lên: 19/06/2014, 22:20

... levels in the serum samples in this study raised the issue of whether the two antibody measures may essentially be the same Depleting the samples of anti-monomer antibodies would not necessarily ... with this approach Methods Serum samples Serum samples were obtained from the Rush Alzheimer s Disease Center (Chicago, IL) from individuals whose diagnosis on the basis of post-mortem clinical ... not support the hypothesis that decreased levels of these antibodies may contribute to AD pathogenesis List of abbreviations used AD: Alzheimer s disease; ApoE: apolipoprotein E; BSA: bovine serum...

Ngày tải lên: 19/06/2014, 22:20

... other systems [55-57] It remains to be determined whether these mechanisms or others could be responsible for the observed elevations of endogenous APP and BACE1 in astrocytes To gain insight into ... cell lysate samples were stored at -80°C until analysis Inhibitor treatments Inhibitors were prepared as concentrated stock solutions according to respective manufacture s instructions The final ... vicious cycle Evidence in favor this hypothesis exists, in that Ab42 is capable of stimulating astrocytes to secrete proinflammatory cytokines, and conversely cytokine combinations that include...

Ngày tải lên: 19/06/2014, 22:20

... AD pathogenesis Therapeutic studies in AD models Access to good animal models is crucial to success in developing disease- modifying therapeutics However, AD neuropathology is incomplete in the ... hypothesis comes mainly from studies of families in which AD is inherited as a dominant trait due to mutations in APP, PS1 or PS2 The evidence that the theory applies to sporadic AD is less solid, ... Ab in brain was similar in single- and doubletransgenic mice [96] The findings are relevant to the Lewy body variant of AD with a-synuclein inclusions Instead of cross-breeding two single-transgenic...

Ngày tải lên: 16/02/2014, 09:20

... were the main contributors (2) A visuospatial/cognitive factor, in which visuospatial and tests of reasoning were the main contributors These included the Rosen Drawing Test [45], matching and ... among individuals with and without an APOE-␧4 allele Please note The intervals on the X axis represent the average time of follow-up assessments after baseline These are smoothed regression lines ... elderly individuals without AD or QD, but other cognitive skills remained stable Increased age was associated with lower scores in all cognitive domains while increased education was associated...

Ngày tải lên: 05/03/2014, 21:20

... cognitive functioning Cognitive screening includes using validated screening instruments, such as the MMSE, and brief bedside assessments Cognitive screenings are usually sensitive to significant cognitive ... other diagnostic tests yield inconclusive findings Neuropsychological Testing A neuropsychological evaluation consists of administering a battery of standardized tests to assess cognition Test ... difficult to distinguish from Parkinson s disease, but the parkinsonism in DLB differs from Parkinson s disease by being more often symmetric, with less pronounced tremor (if any) Hallucinations are...

Ngày tải lên: 05/03/2014, 23:20

... Importantly, this complements data from rat tissues showing that calcineurin is also expressed in neurons [14,15] RCAN1 gene expression is significant in several tissues, particularly human brain, spinal ... serine–threonine protein phosphatase calcineurin [5] The brain is an especially interesting organ in which to examine RCAN1 expression, because calcineurin is highly expressed in this organ, comprising approxi- ... differences in function or localization of these isoforms in the brain In order to try to understand how these isoforms may differ, we examined the expression of the isoforms known to be transcribed in...

Ngày tải lên: 16/03/2014, 11:20

... weak in all of these areas as compared with the AD brain sections (data not shown) In AD brain, immunostainings with the antibody against p-eEF2 at Thr56 showed moderate to strong staining in the ... that subsequently blocks eEF2 binding to ribosomes, resulting in decreased rates of protein synthesis Dephosphorylation of eEF2 relieves its translational restriction and accelerates the translation ... Foundation, SADF (Insamlingsstiftelsen for ¨ Alzheimer- och Demensforskning), Socialstyrelsens Stiftelser, Stiftelsen for Alderssjukdomar, and Svenska ¨ ˚ Lakaresallskapet ¨ ¨ FEBS Journal 272...

Ngày tải lên: 16/03/2014, 22:20

... assessment also included the Alzheimer s Disease Assessment Scale (ADAS-cog 85 points), clock test, cube copying test and A Quick Test of cognitive speed (AQT) These results were taken into consideration ... and a specificity of 87% in a large MCI study population [15] Statistics Statistical analysis was performed using the PASW software (former SPSS software, version 17.0.1 for Windows, SPSS Inc., ... Neuropathological Assessment of Alzheimer s Disease: Consensus recommendations for the postmortem diagnosis of Alzheimer s disease Neurobiol Aging 1997, 18 :S1 -2 40 Saarela MS, Lehtimaki T, Rinne JO, Hervonen...

Ngày tải lên: 22/03/2014, 14:20

... Discussion In the present study, Ab protofibril levels in young and aged animals were assessed in three different AD mouse models Ab protofibrils were present in both the brain and CSF of tg-ArcSwe ... these measures inversely correlated to escape latency at the last day of training (see Fig S2 ), suggesting that spatial search strategies were used by most of the animals Four individuals (two ... crossings The escape latency at the last trial of training was subtracted from mean escape latency at the first day of training, to measure the improvement in spatial learning Thigmotaxis, circling...

Ngày tải lên: 23/03/2014, 06:20

... apoptosis in astrocytes In this model of astrocyte apoptosis, translocation of the NF-kB p65 subunit to the nucleus is observed These findings indicate that, in this case, NF-jB acts as a death-promoting ... a possible cascade of events involving three protease systems: calpain-induced cathepsin release, cathepsin-mediated caspase activation and caspase-mediated calpastatin degradation leading to ... that has been implicated in neuronal cell death [7] (Fig 1) Cross-talk between calpains and caspases The striking similarity between the substrates for caspases and calpains raises the possibility...

Ngày tải lên: 23/03/2014, 10:21

... of increased levels of cytokines in the brains of Alzheimer' s disease patients, and in transgenic mouse models of Alzheimer' s disease [10-12] However, all these reports have focused on a small ... control, PS1, TgAPPsw and PS1/APPsw mouse brain slices was assessed using the Bioplex cytokine multi-array system Cytokine levels were not significantly elevated in PS1 brain slices compared to control ... trols, indicating the absence of an anti-inflammatory response All of the cytokines that were increased in the TgAPPsw brain slices (IL-1α, TNF-α, GM-CSF and IL-6) were further increased in the PS1/APP...

Ngày tải lên: 19/06/2014, 22:20

... text Quantitative comparisons were performed on sections processed at the same time Single ANOVA statistical analysis was used to assess the significance of the differences in plaque area, glial ... adjuvant plus pertussis toxin in thioflavine positive plaques (Figure 2A and 2B) or any of the markers tested below To assess total amyloid deposits in the APP transgenic mice after the month regime ... processes of image acquisition and data management labor-intensive, but the mechanics of analysis itself can introduce some subjectivity Automated digital imaging systems, such as the one tested...

Ngày tải lên: 19/06/2014, 22:20

... from the levels of the two extreme groups Similar results were obtained when the analysis was carried out using LSS scores as proxy of status (p < 0.025, lowest vs highest LSS scores) As shown in ... disease (AD), oxidative stress is one of the earliest events occurring prior to the onset of symptoms and it has been recognised as an essential contributor to the pathogenesis and progression ... catalase or GPx Some of these components may also be induced by stress, thus increasing the flexibility of the anti-oxidant defence system to react to unfavourable conditions Decreases in the levels...

Ngày tải lên: 19/06/2014, 22:20

... http://www.jneuroinflammation.com/content/3/1/30 kinases Lyn and Fyn as well as the tyrosine kinase Syk [30,32,52] Activation of these signaling cascades are linked to the synthesis and secretion of proinflammatory molecules and cytokines ... incidence among patient populations receiving statin treatment [117,118] Despite these promising findings, the use of statins in prospective clinical trials has yielded unsatisfactory results, ... astrocytes results in their extensive exposure to Aβ from the earliest stages of the disease Indeed, reactive astrocytes are found adjacent to senile plaques Plaque-associated astrocytes upregulate the...

Ngày tải lên: 19/06/2014, 22:20

... Numerous clinical and animal reports in the past showed an increase in circulating pro-inflammatory cytokines in the serum of patients and small animals suffering from arthritis [40] To this end, ... following the course of osteoarthritis development in this mouse model [23] Consistent with these findings, real-time qRT-PCR analysis of inflammation-associated mRNAs in the mouse brain demonstrated ... neighboring section The first sections on each glass slide represented the anterior portion of the brain, the next sections the middle and the last sections represented the posterior third of the...

Ngày tải lên: 19/06/2014, 22:20

... Disorders and Stroke and the Alzheimer s disease and Related Disorders Association (NINCDS-ADRDA) [14] All AD cases were defined as sporadic because family histories showed no mention of first-degree ... all results Statistical analysis Hardy-Weinberg equilibrium was assessed using the Chi-square test Genotype and allele distributions were compared using the Chi-square test Differences in allele ... carriers the genetic effect is determined by this strong susceptibility factor There is overlap in the study populations used in present study and in our previous study [9] Linkage disequilibrium...

Ngày tải lên: 19/06/2014, 22:20