clinical+heterogeneity+in+alzheimer+s+disease

... 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 Ab-expressing ... cross-breeding experiments is strengthened if expression and deletion of the gene (s) results in the opposite outcome, or if the results are substantiated by in vitro studies or analyses of clinical samples ... by crossing PDGF–a-synuclein and APP-SweInd, which led to a 1.6-fold increase in a-synuclein inclusions in comparison with transgenic mice that expressed only wild-type human a-synuclein Similar...

Ngày tải lên: 16/02/2014, 09:20

... either polyglutamine or polyalanine expansions in Huntington disease, Huntington related diseases, and various forms of a-synuclein associated with Parkinson disease and synucleinopathies [27] Taken ... Foundation, SADF (Insamlingsstiftelsen for ¨ Alzheimer- och Demensforskning), Socialstyrelsens Stiftelser, Stiftelsen for Alderssjukdomar, and Svenska ¨ ˚ Lakaresallskapet ¨ ¨ FEBS Journal 272 ... eEF2 in its N-terminus (Thr56) that subsequently blocks eEF2 binding to ribosomes, resulting in decreased rates of protein synthesis Dephosphorylation of eEF2 relieves its translational restriction...

Ngày tải lên: 16/03/2014, 22:20

... findings to the human disorders, distinct differences remain These models may be appropriate for studying some aspects of a disease process, while less suitable for others To determine the significance ... celecoxib in the treatment of progression of Alzheimer' s disease [abstract] Sixth International Stockholm/Springfield Symposium on Advances in Alzheimer Therapy 2000:180 Van Gool WA, Weinstein HC, Scheltens ... the Alzheimer' s disease brain Brain Res Mol Brain Res 2000, 81:7-18 Janus C, Phinney AL, Chishti MA, Westaway D: New developments in animal models of Alzheimer' s disease Curr Neurol Neurosci...

Ngày tải lên: 19/06/2014, 22:20

... Demographic characteristics of the cases used in this study Shown are differences between groups of the cases used in this study [PMI post-mortem interval, SD standard deviation] Braak score for neurofibrillary ... 25 26 Pasinetti GM, Aisen PS: Cyclooxygenase-2 expression is increased in frontal cortex of Alzheimer' s disease brain Neuroscience 1998, 87:319-324 Combrinck M, Williams J, De Berardinis MA, Warden ... Braak stage instead of being defined as control or AD Other, previously described [17], discrepancies are most likely due to differences in pathological disease state and investigated brain area,...

Ngày tải lên: 19/06/2014, 22:20

... out using LSS scores as proxy of status (p < 0.025, lowest vs highest LSS scores) As shown in Figure 2, high serum AOC levels predicted a longer survival of AD patients (CPHR, co-varying MMSE scores, ... deficit, we used the MMSE scores as proxy of status (control vs AD) and of disease progression Subjects were divided into three mutually exclusive groups ranked by increasing MMSE scores [below 20 ... participants grouped according to Serum AOC levels in participants grouped according to MMSE scores Square and circle symbols indicate controls and Alzheimer' s disease patients, respectively...

Ngày tải lên: 19/06/2014, 22:20

... global inhibition of src-family tyrosine kinases or inhibition of phosphatidylinositol-3 kinase (PI3K) attenuates ROS production These findings suggest that these kinases are involved in upstream signaling ... functional events in Alzheimer' s disease J Alzheimers Dis 2004, 6:171-175 Markesbery WR: Oxidative stress hypothesis in Alzheimer' s disease Free Radic Biol Med 1997, 23:134-147 Shimohama S, Tanino H, ... proinflammatory responses that act in concert to promote the progressive pathophysiology associated with this disease The results summarized in this review suggest that ROS and iNOS released through...

Ngày tải lên: 19/06/2014, 22:20

... years is 29% compared to 7% in older control cases For AD cases, the incidence of APOE4 in cases younger than 80 years is 57% compared to 29% in older AD cases Page of Discussion In this study, ... measured Assessments for different antibodies were performed in adjacent sections and blind to the pathological and clinical categorization Statistical analyses The Kruskall-Wallis test was used to ... demographic information, disease duration, neuropathological staging and APOE genotype of control and AD cases used in this study Case Diagnosis Sex Age (years) GDS Braak Brain weight (grs) PMD (hours:...

Ngày tải lên: 19/06/2014, 22:20

... subentities, making a clear definition very difficult The majority of AD researchers assume Risk Factors for Disease Progression in Alzheimer' s Disease a linear slope, but some investigators also suggest ... Cardiovascular disease risk factors and progression of Alzheimer s disease Dement Geriatr Cogn Disord., 27(3), 240-246 Risk Factors for Disease Progression in Alzheimer' s Disease 13 Adak, S. , Illouz, ... Diagnosis in Alzheimer s Disease 207 Inga Zerr, Lisa Kaerst, Joanna Gawinecka and Daniela Varges Chapter 11 Alzheimer s Diseases: Towards Biomarkers for an Early Diagnosis Benaïssa Elmoualij, Ingrid...

Ngày tải lên: 28/06/2014, 05:20

... neurological, psychiatric and neuropsychological assessments were reviewed in a consensus conference comprised of neurologists, psychiatrists, and neuropsychologists Based on this review all participants ... cognitive skills remained stable Increased age was associated with lower scores in all cognitive domains while increased education was associated with higher scores APOE-␧4 was not associated with ... allele Please note The intervals on the X axis represent the average time of follow-up assessments after baseline These are smoothed regression lines that depict the differences in the slope of...

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 ... toward scan interpretation that integrates the visual and quantifying information present in clinical PET scans Visual Assessment Systematic visual examination of a clinical brain PET scan involves ... Parkinson s disease by being more often symmetric, with less pronounced tremor (if any) Hallucinations are also more prominent in Parkinson s disease than in DLB The diagnosis is supported by a history...

Ngày tải lên: 05/03/2014, 23:20

... 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 cord, kidney, liver, ... control tissues (a representative western blot is shown in Fig 3A) As human brain tissue is difficult to obtain, we focused on the most interesting regions for further studies These regions included ... shown to bind to and inhibit the serine–threonine protein phosphatase calcineurin [5] The brain is an especially interesting organ in which to examine RCAN1 expression, because calcineurin is...

Ngày tải lên: 16/03/2014, 11:20

... present study was set slightly higher than the previously reported community-based mean values In the present study the cognitive assessment also included the Alzheimer s Disease Assessment Scale ... dysfunction Abbreviations Ab: b-amyloid; AD: Alzheimer s disease; ADAS-cog: Alzheimer s Disease Assessment Scale; APOE: apolipoprotein E; AQT: A Quick Test of cognitive speed; CSF: cerebrospinal ... PASW software (former SPSS software, version 17.0.1 for Windows, SPSS Inc., Chicago, IL, USA) Non-parametric tests were used because normal distribution could not be assumed in the groups Spearman...

Ngày tải lên: 22/03/2014, 14:20

... family-based study, but varied in subsequent reports, depending on sample size, study design, inclusion of probands in the analysis and methods of calculation To address some of these issues, Healy ... other social issues Genetic testing should preferably be supported by a multidisciplinary team with expertise in handling pre-testing and post-testing related problems A recent study has demonstrated ... a haplotype that increases disease risk when present in two copies was identified among sporadic Chinese PD population in Singapore [32] However, other studies did not reveal association with any...

Ngày tải lên: 23/03/2014, 04:20

... contrast, in transgenic mice, functional deficits and loss of synapses are, at least in some models, observed in young transgenic animals devoid of plaque deposits, suggesting that soluble Ab species ... 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 ... conclusions drawn from such future studies in aged tg-ArcSwe mice would obviously not be straightforward because Ab burden and insoluble Ab are also increased The present study only suggests that...

Ngày tải lên: 23/03/2014, 06:20

... cathepsins, which are implicated in neuronal cell death He suggested a possible cascade of events involving three protease systems: calpain-induced cathepsin release, cathepsin-mediated caspase ... between calpains and caspases The striking similarity between the substrates for caspases and calpains raises the possibility that both protease families contribute to structural dysregulation ... death in cultured rat astrocytes These findings suggest that calpain is involved in Ca2+-mediated apoptosis in astrocytes In this model of astrocyte apoptosis, translocation of the NF-kB p65 subunit...

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 ... Circulating cytokines in Alzheimer' s disease J Psychiatr Res 1997, 31:657-60 Tarkowski E, Wallin A, Regland B, Blennow K, Tarkowski A: Local and systemic GM-CSF increase in Alzheimer' s disease and...

Ngày tải lên: 19/06/2014, 22:20

... memory loss in a mouse transgenic model of Alzheimer' s disease J Neurosci 2002, 22:6331-6335 Selkoe DJ, Schenk D: Alzheimer' s disease: molecular understanding predicts amyloid-based therapeutics Annu ... reagent that stains proteins in beta sheet conformation [31] Therefore, the accumulation of thioflavine stained plaques in animals immunized at ages 12–16 months was assessed in hippocampus and cortical ... was performed on freefloating brain sections To stain for Aβ plaques, sections were immersed in 50% formic acid for Endogenous peroxidase in tissue was blocked by treating with 3% H2O2 in PBS,...

Ngày tải lên: 19/06/2014, 22:20

... 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 ... encouraging results were obtained in two clinical trials in which IvIg was administered to AD patients [22,23] and a multi-site phase trial is in progress In our ELISA studies we found that in addition ... increased in AD vs NCI sera (by 20% in undissociated samples and 29% in dissociated samples) 95% Tukey confidence intervals for differences in the mean antibody levels indicated that the possibility...

Ngày tải lên: 19/06/2014, 22:20

... Bonotis K, et al: Systemic immune aberrations in Alzheimer s disease patients J Immunol 2008, 193:183-187 Holmes C, et al: Systemic inflammation and disease progression in Alzheimer disease Neurol ... Massive gliosis induced by interleukin-6 suppresses Aβ deposition in vivo: evidence against inflammation as a driving force for amyloid deposition FASEB 2004, 24:548-559 19 Shaftel SS, et al: Sustained ... 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,...

Ngày tải lên: 19/06/2014, 22:20

... detailed study is necessary Delirium is regarded as syndrome that consists of several domains of symptoms, such as disturbance of consciousness, cognitions, and perceptions [17] At present, it is unclear ... Conclusions These two cases suggest that fluvoxamine could be an alternative approach in treating delirium of patients with Alzheimer s disease because of the risk of extrapyramidal side effects ... is currently stable Discussion To our knowledge, this is the first report demonstrating that fluvoxamine monotherapy is effective for treating the delirium of patients with Alzheimer s disease...

Ngày tải lên: 08/08/2014, 23:21