It has been suggested that cytokine-mediated inflammation plays a key role for the onset and/or development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). However, clinical studies have yielded inconsistent results for the aberrant cytokine levels in circulation of patients with AD, PD, and ALS. Previous studies have used meta-analysis to address the inconsistent data for blood cytokine levels in the patients with AD, PD, and ALS. Here, we performed a systemic review of cerebrospinal fluid inflammatory cytokine data in patients with AD, PD and ALS, and sought to quantitatively summarize the CSF inflammatory cytokine data with a meta-analytical technique. The systematic search from Pubmed and Web of Science identified 71 articles with 2629 patients and 2049 controls for the meta-analysis. Random-effects meta-analysis demonstrated that CSF TGF-β, MCP-1, and YKL-40 levels were significantly elevated in AD patients when compared with controls. In addition, patients with PD had heightened levels of TGF-β1, IL-6, and IL-1β in CSF. Furthermore, G-CSF, IL-2, IL-15, IL-17, MCP-1, MIP-1α, TNF-α, and VEGF levels were significantly increased in patients with ALS as compared with controls. Taken together, these results not only strengthen the clinical evidence that neurodegenerative diseases are accompanied by the increased inflammatory response, but also reveal the unique inflammatory response profile in the central nervous system of patients with AD, PD and ALS. Given the robust associations between some cytokines and neurodegenerative diseases found in this meta-analysis, CSF inflammatory cytokines may be used as biomarkers for these diseases in the future.

Accumulating evidence suggest that aberrations of neurotrophic factors are involved in the etiology and pathogenesis of Alzheimer's disease (AD), but clinical data were inconsistent. Therefore, a meta-analysis on neurotrophic factor levels in AD is necessary. We performed a systematic review of blood, CSF, and post-mortem brain neurotrophic factor levels in patients with AD compared with controls and quantitatively summarized the clinical data in blood and CSF with a meta-analytical technique. A systematic search of PubMed and Web of Science identified 98 articles in this study (with samples more than 9000). Random effects meta-analysis demonstrated that peripheral blood BDNF levels were significantly decreased in AD patients compared with controls. However, blood NGF, IGF, and VEGF did not show significant differences between cases and controls. In CSF, random effects meta-analysis showed significantly deceased BDNF and increased NGF levels in patients with AD, whereas IGF and VEGF did not show significant differences between the AD group and control group. In addition, 23 post-mortem studies were included in the systematic review. Although data from post-mortem brains were not always consistent across studies, most studies suggested decreased BDNF and increased (pro)NGF levels in hippocampus and neocortex of patients with AD. These results provide strong clinical evidence that AD is accompanied by an aberrant neurotrophin profile, and future investigations into neurotrophins as biomarkers (especially CSF BDNF and NGF) and therapeutic targets for AD may be warranted.

BackgroundThe association between Down syndrome and celiac disease has been reported by many studies. However, the prevalence of celiac disease (CD) in Down syndrome (DS) varies considerably across studies (from 0 % to 19 %). The aim of this study was to use meta-analysis to exam the prevalence of CD in patients with DS.MethodsA systematic search of English articles from Pubmed, Web of Science and CNKI without year limitation. Data were extracted by two independent observers and pooled using a random effects model by the Comprehensive Meta-Analysis Version 2 software.ResultsA pooled analysis, based on 31 studies included 4383 individuals, revealed prevalence of biopsy-confirmed CD of 5.8 % (95 % CI = 4.7-7.2 %) in patients with DS. Sub-group analysis showed a slightly higher prevalence of CD in children with DS (6.6 %; 17 studies), than in age mixed samples with both children and adults (5.1 %; 13 studies). In addition, most of the studies included in this meta-analysis were from Europe and America, with the prevalence of celiac disease of 6 % (21 studies) and 5.7 % (6 studies) in DS patients, respectively. Furthermore, meta-regression analysis suggested that proportion of antibody-positive individuals that underwent small intestine biopsy had moderating effect on the outcome of the meta-analysis.ConclusionsThese results demonstrated that patients (children) with Down syndrome had high prevalence of CD (more than one in twenty). The prevalence is high enough to motivate screening CD in DS children.