Inverse association of cortisol serum levels with T-tau,P-tau 181 and P-tau 231 peptide levels and T-tau/Aβ 1–42 ratios in CSF in patients with mild Alzheimer’s disease dementia

Hypercortisolemia and increased levels of hyperphosphorylated tau proteins in cerebrospinal fluid (CSF) are common features with pathogenic relevance in Alzheimer`s disease (AD). Experimental studies point to an influence of cortisol on Aβ and tau pathology in AD. Association of both parameters have not yet been described in a sample of AD patients. In the present study, serum levels of cortisol were determined in 26 patients with mild AD dementia and 20 age-matched healthy elderly controls by ELISA. In addition, we measured in AD patients CSF levels of cortisol, total tau (T-tau), tau phosphorylated at threonine 181 (P-tau 181), tau protein phosphorylated at threonine 231 (P-tau 231) and beta-Amyloid (Aβ) 1–42 and determined T-tau/Aβ 1–42 ratios in CSF. We found in AD patients significantly increased cortisol serum levels (551.4 ± 146.1 nmol/l; P = 0.002) as compared to healthy controls (435.3 ± 83.9 nmol/l). In AD patients, cortisol serum levels were significantly inversely correlated with T-tau (r = −0.496; P = 0.01), P-tau 181 (r = −0.558; P = 0.003) and P-tau 231 (−0.500; P = 0.009) protein levels and T-tau/Aβ 1–42 ratios (r = −0.450; P = 0.021) in CSF. In addition, cortisol serum levels showed a trend of positive correlation with Aβ 1–42 CSF levels (r = 0.386; P = 0.052). However, no significant correlations of cortisol serum with CSF levels as well as cortisol CSF levels with CSF biomarkers could be detected in AD patients. In conclusion, our results show that increased cortisol serum but not CSF levels are associated with minor signs of AD pathology in CSF, indicating a putative neuroprotective effect of moderately elevated cortisol serum levels in patients with mild AD dementia.     

Serum levels of cytokines and C-reactive protein in acute ischemic stroke patients,and their relationship to stroke lateralization,type, and infarct volume

There is increasing evidence that inflammation plays an important role in the progression of acute ischemic stroke (AIS). The primary aims of this study were to examine the serum levels of 13 cytokines, C-reactive protein (CRP), glucose, and hemoglobin in AIS patients, and their relationship to stroke lateralization, type, and infarct volume. Forty-five patients with AIS were evaluated. Blood samples were taken within 72 h, and volumetric analyses performed within 1–7 days after AIS onset. Cytokines were measured in serum from all patients and from 40 control subjects using Luminex Bio-Plex XMap technology. The levels of interleukin (IL)-1ra (p < 0.001), IL-6 (p < 0.001), IL-8 (p < 0.001), IL-9 (p = 0.038), IL-10 (p = 0.001), IL-12 (p = 0.001), IL-18 (p < 0.001), and GRO-α (CXCL1) (p = 0.017) were significantly higher in the AIS patients than in the controls. The IL-8 level was significantly correlated with age in the patient group (r = 0.52, p < 0.001). None of the variables were found to be associated with stroke lateralization. Infarct volume was significantly positively correlated with CRP level (r = 0.47, p = 0.005). Patients with radiologically confirmed infarctions had significantly elevated serum levels of GRO-α (p = 0.023). The cytokine profile of the AIS patients supports not only earlier findings of a proinflammatory response but also early activation of endogenous immunosuppressive mechanisms. Novel findings of this study are elevated serum levels of IL-9 and GRO-α. Elevated GRO-α in AIS patients with radiologically confirmed infarctions suggests that GRO-α is specific for stroke of known etiology. Our results indicate that CRP plays an important role in the progression of cerebral tissue injury.     

Serum macrophage migration inhibitory factor levels are associated with infarct volumes and long-term outcomes in patients with acute ischemic stroke

Purpose: Previous studies have shown that macrophage migration inhibition factor (MIF) plays a significant role in stroke. The aim of this study was to investigate the association of the serum MIF level with both infarct volume and long-term outcome in patients with acute ischemic stroke (AIS). Methods: This study included 146 patients who were identified within 24 h of first experiencing AIS symptoms. Serum MIF levels were tested at the time of admission and three months later. Logistic regression was used to evaluate the risk and long-term outcome of stroke according to serum MIF level. Results: Serum MIF levels were only higher in acute-stage AIS patients compared with those of the normal controls (p < 0.0001). Chronic-stage serum MIF levels were significantly lower than acute-stage serum MIF levels (p < 0.001) and were similar to serum MIF levels in the controls (p = 0.392). The serum MIF level was positively associated with infarct volume (r = 0.5515, p < 0.0001) and NIHSS score (r = 0.5190, p < 0.0001). After adjusting for other significant outcome predictors, the serum MIF level was an independent predictor of long-term outcome, with an adjusted OR of 1.113 (p = 0.005, 95% CI: 1.051–1.238). Conclusions: This study demonstrated that serum MIF levels were significantly increased after AIS. Serum MIF levels at admission were positively correlated with infarct volume and long-term outcome in patients with AIS. The serum MIF level could serve as a useful prognostic marker in patients with AIS.     

CSF phosphorylated tau is a possible marker for discriminating Alzheimer's disease from dementia with Lewy bodies

Tau and β-amyloid (1–42) (Aβ42) are two independent markers for the early diagnosis of Alzheimer's disease (AD). In the present study, biochemical markers were validated as tools for differential diagnosis between AD and dementia with Lewy bodies (DLB). Tau, Aβ42 and phosphotau (181P) were measured in cerebrospinal fluid (CSF) from controls (n=40) and from patients with AD (n=80) or DLB (n=43) using the HT7-AT270 assay (prototype version). In comparison with AD, in DLB no differences were found for Aβ42 and lower phospho-tau. ROC analysis was used to compare the discriminatory power of total tau with that of phospho-tau. The area under the curve (AUC) amounted to 0.782±0.048 (mean ±SE) for tau and to 0.839±0.042 for phospho-tau (p<0.039) for differentiation of AD from DLB. The present results indicate that CSF phospho-tau may be a good marker for differentiation between AD and DLB.     

Small heat shock protein HspB8: its distribution in Alzheimer’s disease brains and its inhibition of amyloid-β protein aggregation and cerebrovascular amyloid-β toxicity

Alzheimer’s disease (AD) is characterized by pathological lesions, such as senile plaques (SPs) and cerebral amyloid angiopathy (CAA), both predominantly consisting of a proteolytic cleavage product of the amyloid-β precursor protein (APP), the amyloid-β peptide (Aβ). CAA is also the major pathological lesion in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D), caused by a mutation in the gene coding for the Aβ peptide. Several members of the small heat shock protein (sHsp) family, such as αB-crystallin, Hsp27, Hsp20 and HspB2, are associated with the pathological lesions of AD, and the direct interaction between sHsps and Aβ has been demonstrated in vitro. HspB8, also named Hsp22 of H11, is a recently discovered member of the sHsp family, which has chaperone activity and is observed in neuronal tissue. Furthermore, HspB8 affects protein aggregation, which has been shown by its ability to prevent formation of mutant huntingtin aggregates. The aim of this study was to investigate whether HspB8 is associated with the pathological lesions of AD and HCHWA-D and whether there are effects of HspB8 on Aβ aggregation and Aβ-mediated cytotoxicity. We observed the expression of HspB8 in classic SPs in AD brains. In addition, HspB8 was found in CAA in HCHWA-D brains, but not in AD brains. Direct interaction of HspB8 with Aβ_1–42, Aβ_1–40 and Aβ_1–40 with the Dutch mutation was demonstrated by surface plasmon resonance. Furthermore, co-incubation of HspB8 with D-Aβ_1–40 resulted in the complete inhibition of D-Aβ_1–40-mediated death of cerebrovascular cells, likely mediated by a reduction in both the β-sheet formation of D-Aβ_1–40 and its accumulation at the cell surface. In contrast, however, with Aβ_1–42, HspB8 neither affected β-sheet formation nor Aβ-mediated cell death. We conclude that HspB8 might play an important role in regulating Aβ aggregation and, therefore, the development of classic SPs in AD and CAA in HCHWA-D.     

The effect of thrombolysis on short-term improvement depends on initial stroke severity

A large number of parameters have been identified as predictors of early outcome in patients with acute ischemic stroke. In the present work we analyzed a wide range of demographic, metabolic, physiological, clinical, laboratory and neuroimaging parameters in a large population of consecutive patients with acute ischemic stroke with the aim of identifying independent predictors of the early clinical course. We used prospectively collected data from the Acute Stroke Registry and Analysis of Lausanne. All consecutive patients with ischemic stroke admitted to our stroke unit and/or intensive care unit between 1 January 2003 and 12 December 2008 within 24 h after last-well time were analyzed. Univariate and multivariate analyses were performed to identify significant associations with the National Institute of Health Stroke Scale (NIHSS) score at admission and 24 h later. We also sought any interactions between the identified predictors. Of the 1,730 consecutive patients with acute ischemic stroke who were included in the analysis, 260 (15.0%) were thrombolyzed (mostly intravenously) within the recommended time window. In multivariate analysis, the NIHSS score at 24 h after admission was associated with the NIHSS score at admission (β = 1, p < 0.001), initial glucose level (β = 0.05, p < 0.002) and thrombolytic intervention (β = −2.91, p < 0.001). There was a significant interaction between thrombolysis and the NIHSS score at admission (p < 0.001), indicating that the short-term effect of thrombolysis decreases with increasing initial stroke severity. Thrombolytic treatment, lower initial glucose level and lower initial stroke severity predict a favorable early clinical course. The short-term effect of thrombolysis appears mainly in minor and moderate strokes, and decreases with increasing initial stroke severity.     

Serum cytokine and glucose levels as predictors of poststroke fatigue in acute ischemic stroke patients

Fatigue is a common but often overlooked symptom after stroke. This study investigated whether stroke type, infarct volume, and laterality, as well as the levels of various cytokines and other blood components in the acute phase of acute ischemic stroke (AIS), can predict the level of fatigue at 6, 12, and 18 months after its onset. In 45 patients with acute stroke, serum levels of C-reactive protein, hemoglobin, glucose, and 13 cytokines were measured within 72 h of stroke onset. The cytokine measurements were performed using BioPlex XMap technology (Luminex). The acute serum levels of interleukin (IL)-1β and glucose were positively correlated with the score on the Fatigue Severity Scale (FSS) at 6 months after the stroke (r = 0.37, p = 0.015, and r = 0.37, p = 0.017, respectively). The acute serum levels of IL-ra and IL-9 were negatively correlated with FSS score at 12 months after the stroke (r = −0.38, p = 0.013, and r = −0.36, p = 0.019, respectively). The FSS score at 12 months after stroke was significantly lower in patients with radiologically confirmed infarction than in those without such confirmation (p = 0.048). The FSS score at 18 months was not correlated with any of the measured variables. High acute serum levels of glucose and IL-1β, and low IL1-ra and IL-9 may predict fatigue after AIS, indicating that the development of poststroke fatigue can be accounted for by the proinflammatory response associated with AIS. These novel findings support a new cytokine theory of fatigue after stroke. However, more research is needed to validate the results of this study.     

Prospective study on association between plasma amyloid beta-42 and atherosclerotic risk factors

An association between plasma Amyloid beta peptides (Aβ) with blood lipids was reported in cross-sectional studies. The present study examined the 5-year prospective association of atherosclerotic risk factors with plasma Aβ42 in 440 elderly persons without both Alzheimer’s disease (AD) or mild cognitive impairment (MCI) at baseline. Persons in the highest tertile of total cholesterol (TC) or LDL-C at baseline showed low plasma Aβ42 at 5 years. Regression analysis confirmed TC and LDL-C as negative predictors of Aβ42 (p = 0.001). An increase over 5 years of HDL-C was a negative predictor and the presence of an APOE ε4 allele was a positive predictor for decrease of Aβ42 in converters to MCI. In converters to AD, increase of both TC and of HbA1c were positive predictors of Aβ42 levels at 5 years. Analysis of covariance showed a positive association between Δ-TC, Δ-LDL-C, Δ-HbA1c, and levels of Aβ42 at 5 years (p = 0.006; 0.013 and 0.027 resp.) in converters to AD independently on lipid-lowering treatment. The association of vascular risk factors TC, LDL-C, and HbA1c with higher Aβ42 levels might, after confirmation in other cohorts, influence the development of lifestyle interventions concerning plasma Aβ42 and AD.     

Reduced CSF carboxyterminally truncated Aβ peptides in frontotemporal lobe degenerations

Summary. Cerebrospinal fluid (CSF) carboxyterminally truncated amyloid-beta (Aβ) peptides, Aβ1-42 and tau protein were evaluated in 30 patients with frontotemporal lobe degenerations (FTLD), 30 Alzheimer’s disease (AD) patients and 30 non-demented disease controls (NDC) by Aβ-SDS-PAGE/immunoblot as well as commercial ELISAs for Aβ1-42 and total tau. FTLD displayed a significant drop of Aβ1-37 (p = 2.7 × 10⁻⁴), Aβ1-38 (p = 4.2 × 10⁻⁵) and Aβ1-42 (p = 3.3 × 10⁻⁴). Aβ1-42 was selectively decreased in AD (p = 8.5 × 10⁻¹⁰). Decreased Aβ1-38 enabled contrasts of beyond 85% to distinguish FTLD from AD and NDC patients, alone or in combination. Accordingly, low CSF Aβ1-37 and Aβ1-38 represent a biomarker candidate for FTLD and may reflect disease-specific changes of APP metabolism. Further validation should be carried out on dementias other than AD, diagnostically relevant control groups without dementia and without any evident affection of the central nervous system and subgroups of FTLD. Moreover, independent methods of measurement should be applied to CSF Aβ1-38.     

Cerebrospinal fluid diagnostic markers correlate with lower plasma copper and ceruloplasmin in patients with Alzheimer’s disease

Summary. Increasing evidence links Alzheimer’s disease (AD) with misbalanced Cu homeostasis. Recently, we have shown that dietary Cu supplementation in a transgenic mouse model for AD increases bioavailable brain Cu levels, restores Cu, Zn-super oxide-1 activity, prevents premature death, and lowers Aβ levels. In the present report we investigated AD patients with normal levels of Aβ42, Tau and Phospho-Tau in the cerebrospinal fluid (CSF) in comparison with AD patients exhibiting aberrant levels in these CSF biomarkers. The influence of these cerebrospinal fluid (CSF) diagnostic markers with primary dependent variables blood Cu, Zn and ceruloplasmin (CB) and secondary with CSF profiles of Cu, Zn and neurotransmitters was determined. Multivariate tests revealed a significant effect of factor diagnostic group (no AD diagnosis in CSF or AD diagnosis in CSF) for variables plasma Cu and CB (F = 4.80; df = 2, 23; p = 0.018). Subsequent univariate tests revealed significantly reduced plasma Cu (−12.7%; F = 7.05; df = 1, 25; p = 0.014) and CB (−14.1%; F = 9.44; df = 1, 24; p = 0.005) levels in patients with aberrant CSF biomarker concentrations. Although only AD patients were included, the reduced plasma Cu and CB levels in patients with a CSF diagnosis of advanced AD supports previous observations that a mild Cu deficiency might contribute to AD progression. The first and second author contributed equally     

Combined CSF tau, p-tau181 and amyloid-β 38/40/42 for diagnosing Alzheimer’s disease

Cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ) 1-38, 1-40, 1-42, total-tau and phospho-tau in samples from 156 patients with Alzheimer’s disease (AD) (n = 44), depressive cognitive complainers (DCC, n = 25) and various other forms of non-Alzheimer dementias (NAD, n = 87) were analyzed by electrochemiluminescence and enzyme linked immunosorbent assay, respectively. A significant decrease of CSF Aβ1-42 was the most powerful single marker for differentiation of AD from DCC, yielding accuracies of beyond 85%. Increased p-tau and the ratio Aβ1-42/Aβ1-38 yielded accuracies of beyond 80 and 85%, respectively, to discriminate AD versus NAD. Combining p-tau with Aβ1-42/Aβ1-38 resulted in a sensitivity of 94% for detection of AD and 85% specificity for excluding NAD. Decreased CSF Aβ1-42 represents a core biomarker for AD. The lack of specificity for exclusion of NAD can be most effectively compensated by the ratio Aβ1-42/Aβ1-38. The ratio Aβ1-42/Aβ1-38/p-tau powerfully discriminates AD versus NAD and fulfils the accuracy requirements for an applicable screening and differential diagnostic AD biomarker.     

Brain aging and Aβ<Subscript>1–42</Subscript> neurotoxicity converge via deterioration in autophagy–lysosomal system: a conditional <Emphasis Type="Italic">Drosophila</Emphasis> model linking Alzheimer’s neurodegeneration with aging

Aging is known to be the most prominent risk factor for Alzheimer’s disease (AD); however, the underlying mechanism linking brain aging with AD pathogenesis remains unknown. The expression of human amyloid beta 42 peptide (Aβ_1–42), but not Aβ_1–40 in Drosophila brain induces an early onset and progressive autophagy–lysosomal neuropathology. Here we show that the natural process of brain aging also accompanies a chronic and late-onset deterioration of neuronal autophagy–lysosomal system. This process is characterized by accumulation of dysfunctional autophagy–lysosomal vesicles, a compromise of these vesicles leading to damage of intracellular membranes and organelles, necrotic-like intraneuronal destruction and neurodegeneration. In addition, conditional activation of neuronal autophagy in young animals is protective while late activation is deleterious for survival. Intriguingly, conditional Aβ_1–42 expression limited to young animals exacerbates the aging process to a greater extent than Aβ_1–42 expression in old animals. These data suggest that the neuronal autophagy–lysosomal system may shift from a functional and protective state to a pathological and deleterious state either during brain aging or via Aβ_1–42 neurotoxicity. A chronic deterioration of the neuronal autophagy–lysosomal system is likely to be a key event in transitioning from normal brain aging to pathological aging leading to Alzheimer’s neurodegeneration.     

Suppressed expression of nicotinic acetylcholine receptors by nanomolar β-amyloid peptides in PC12 cells

Summary. A line of evidence has shown that a link between the common pathological features of β-amyloid peptide (Aβ) deposition and cholinergic degeneration observed in Alzheimer's disease (AD) may exist, however, no experimental evidence has shown that exposure to Aβ can decrease expression of nicotinic acetylcholine receptors (nAChRs), which have been shown to play roles in brain cognitive functions. Here, we report that treatment with Aβ_1–40 and Aβ_25–35 at nanomolar concentrations significantly decreased the [³H]epibatidine and [¹²⁵I]α-bungarotoxin binding sites, the protein and mRNA levels of nAChR α3, α7 and β2 subunits in PC12 cells. Aβ_1–40 and Aβ_25–35 at the concentrations used in the treatment study neither bound to nAChRs nor induced apoptosis, but significantly inhibited the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5,diphenyl tetrazolium bromide) reduction. These data suggest that the decreased biosynthesis of nAChRs induced by Aβ may be attributable partially to perturbances of some intracellular signal transduction pathways. The results presented in this study lead to a hypothesis that Aβ can degenerate nAChRs early in the course of AD before the formation of abundant Aβ fibrils. Received May 3, 2001; accepted August 23, 2001     

Genetic association of BACE1 gene polymorphism C786G with late-onset Alzheimer’s disease in Chinese

β-Amyloid (Aβ) peptides are derived from the end oproteolytic processing of amyloid precursor protein (APP) and play a key role in the pathogenesis of Alzheimer’s disease (AD). β-Site APP-cleaving enzyme 1 ([BACE1] also known as β-secretase) is responsible for cleaving APP to generate neurotoxic Aβ peptides in patients with AD. The BACE1 gene is located on chromosome 11q23.3, near the recently identified region with increased lod scores for AD. The biological functional and genetic association studies indicated that the BACE1 gene might be a genetic risk factor for late-onset Alzheimer’s disease (LOAD). To investigate an association between the BACE1 C786G polymorphism and sporadic LOAD in Chinese, we examined 105 LOAD patients and 130 healthy controls. Our results showed higher frequency of the 786G-allele in LOAD patients (38.6%) than that in controls (28.5%), and a statistical significance was observed for an association of the G-allele with LOAD (odds ratio [OR]=1.58, 95% confidence interval [CI] 1.07–2.23, p=0.02). We also found a synergetic interaction between the G-allele and apolipoprotein E allele 4 (APOE ε4) status on the risk of LOAD (OR=1.91, 95% CI 1.23–2.95, p=0.003). These results suggest that BACE1 gene polymorphism C786G might act as an APOE ε4 allele-dependent risk factor for developing LOAD in Chinese.     

Tauopathies and synucleinopathies: Do cerebrospinal fluid β-amyloid peptides reflect disease-specific pathogenesis?

Summary To evaluate variations in amyloid beta (Aβ) peptide pattern in cerebrospinal fluid (CSF) in neurodegenerative disorders. A recently established quantitative urea-based Aβ-sodium-dodecylsulfate-polyacrylamide-gel-electrophoresis with western immunoblot (Aβ-SDS-PAGE/immunoblot) revealed a highly conserved Aβ peptide (Aβ1-37, 1-38, 1-39, 1-40, 1-42) pattern in CSF. We asked whether the variation might be useful to further elucidate the overlap between or distinctions among neurodegenerative diseases in Aβ-processing. We used the Aβ-SDS-PAGE/immunoblot to investigate CSF for disease-specific Aβ peptide patterns. CSF samples from 96 patients with mainly clinically diagnosed Alzheimer’s disease (n = 15), progressive supranuclear palsy (n = 20), corticobasal degeneration (n = 12), Parkinson’s disease (n = 11), multiple systems atrophy (n = 18), and dementia with Lewy-bodies (n = 20) were analysed as well a comparison group (n = 19). The Aβ peptide patterns varied between tauopathies and synucleinopathies and between all diseases and the comparison group, possibly due to the influence of tau and α-synuclein on Aβ-processing.     

Reduction of aggregated Tau in neuronal processes but not in the cell bodies after Aβ42 immunisation in Alzheimer’s disease

Alzheimer’s disease (AD) pathology is characterised by aggregation in the brain of amyloid-β (Aβ) peptide and hyperphosphorylated tau (phospho-tau), although how these proteins interact in disease pathogenesis is unclear. Aβ immunisation results in removal of Aβ from the brain but cognitive decline continues to progress, possibly due to persistent phospho-tau. We quantified phospho-tau and Aβ42 in the brains of 10 AD patients (iAD) who were actively immunised with Aβ42 (AN1792, Elan Pharmaceuticals) compared with 28 unimmunised AD cases (cAD). The phospho-tau load was lower in the iAD than the cAD group in the cerebral cortex (cAD 1.08% vs. iAD 0.72%, P = 0.048), CA1 hippocampus (cAD 2.26% vs. iAD 1.05%; P = 0.001), subiculum (cAD 1.60% vs. iAD 0.31%; P = 0.001) and entorhinal cortex (cAD 1.10% vs. iAD 0.18%; P < 0.001). Assessment of the localisation within neurons of phospho-tau indicated that the Aβ immunotherapy-associated reduction was confined to neuronal processes, i.e. neuropil threads and dystrophic neurites. However, the phospho-tau accumulation in the neuronal cell bodies, contributing to neurofibrillary tangles, appeared not to be affected. In showing that Aβ immunisation can influence phospho-tau pathology, we confirm the position of Aβ as a target for modifying tau accumulation in AD and demonstrate a link between these proteins. However, the continuing progression of cognitive decline in AD patients after Aβ immunisation may be explained by its lack of apparent effect on tangles.     

The Ca2+/calmodulin-dependent protein kinase II-associated protein complex isolated from chicken retina

Activated microglia represent a major source of inflammatory factors in Alzheimer’s disease and a possible source of cytotoxic factors. β-Amyloid (Aβ) peptide, the predominant component in amyloid plaques, has been shown to activate microglia and stimulate their production of inflammatory factors. The present study was performed to analyze the responses of microglia to different forms of Aβ, with regard to release of the proinflammatory cytokines interleukin-1α (IL-1α), IL-1β, tumor necrosis factor-α (TNF-α), IL-6, and interferon-γ (IFN-γ), as well as the IL-1 receptor antagonist (IL-1ra). Primary cultures of microglia from rat neonatal cerebral cortex were incubated with freshly dissolved Aβ_1–40 or Aβ_1–42, Aβ_1–40 fibrils, Aβ_1–40 βamy balls, or vehicle. Aβ_1–40 fibrils did not significantly stimulate any of these cytokines. Freshly dissolved Aβ_1–40 resulted in a marked increase in the release of IL-1β, and freshly dissolved Aβ_1–42 significantly stimulated both IL-1α and IFN-γ secretion. The Aβ_1–40 βamy balls stimulated the secretion of IL-1α and IL-1β. Incubation with Aβ peptides did not affect the secretion of IL-1ra, IL-6, or TNF-α. In the case of IL-1β, the response is correlated with the presence of Aβ peptide as monomers and oligomers.     

A nationwide study on topography and efficacy of the stroke treatment network in the Czech republic

The SITS (Safe Implementation of Thrombolysis in Stroke)-EAST project was launched in 2007 to support evidence-based stroke treatments, including thrombolytic treatments (TLTs), in Central and Eastern Europe. The aim of this study was to detail the topography, efficacy, and specific characteristics of stroke centers in the Czech Republic (CZ), the country with the highest rate of TLT. The nationwide study was performed between September and November 2007 through a questionnaire sent to all centers registered in SITS. The questionnaire contained 25 questions addressing how centers met recommendations for primary and comprehensive stroke centers in 2006. Center characteristics predicting the number of TLTs were identified by multiple regression analysis. Altogether, data were obtained from 42 centers (88% response rate) with the following characteristics [median (min–max)]: catchment area population 150,000 (90,000–750,000); number of strokes/year 420 (150–1,589); number of TLTs 7.5 (2–45); number of physicians specialized in stroke 3 (1–7). Centers treated 4.3% of the patients with ischemic strokes with tissue plasminogen activator. A stroke unit was present in 32 (78%) departments. Rescue interventional therapies were performed in 11 (26%). Financial problems restricted TLT in 14 (35%) centers. Fourteen factors were associated with the number of TLTs in univariate regression analysis, but in multiple regression analysis, only the catchment area population (p < 0.001), >3 physicians specialized in stroke (p < 0.001), and the presence of an acute interventional program (p < 0.006) remained significant. This study provides the fundamental stroke treatment network data that are essential for certification and further SITS-EAST TLT expansion.