Vascular endothelial growth factor is an effective biomarker for vascular dementia, not for Alzheimer's disease: A meta-analysis.

INTRODUCTION: Vascular pathology is known to contribute to dementia and vascular endothelial growth factor (VEGF) is a well-established biomarker associated with vascular alterations. Nonetheless, research findings on VEGF in Alzheimer's disease (AD) and vascular dementia (VaD) are inconsistent across various studies. METHODS: We conducted a meta-analysis to elucidate relationships between VEGF and AD/VaD. RESULTS: Twenty-four studies were included. Pooled data showed that both blood and cerebrospinal fluid (CSF) VEGF levels were higher in VaD patients, whereas no significant difference was found between AD patients and healthy controls. However, the correlation between blood VEGF and AD was found among studies with AD pathology verification. And blood VEGF levels were higher in AD patients than controls in "age difference < 5 years" subgroup and CSF samples for European cohorts. DISCUSSION: This study highlights that VEGF is more effective for the diagnosis of VaD and vascular factors are also an important contributor in AD. Highlights: Vascular endothelial growth factor (VEGF) levels were higher in the vascular dementia group, but not in the overall Alzheimer's disease (AD) group.Correlation between VEGF and AD was found among studies with clear AD pathological verification.Elevated VEGF in the cerebrospinal fluid might be a diagnostic marker for AD in European populations.

Alzheimer's disease early diagnostic and staging biomarkers revealed by large-scale cerebrospinal fluid and serum proteomic profiling.

Amyloid-ß, tau pathology, and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease (AD). However, these proteins represent only a fraction of the complex biological processes underlying AD, and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic biomarkers. More AD-specific early diagnostic and disease staging biomarkers are needed. In this study, we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid (CSF) and serum samples in a discovery cohort comprising 98 participants. Candidate biomarkers were validated by parallel reaction monitoring-based targeted proteomic assays in an independent multicenter cohort comprising 288 participants. We quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort, identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers, respectively. In the validation cohort, 58 and 21 CSF proteins, as well as 12 and 18 serum proteins, were verified as early diagnostic and staging biomarkers, respectively. Separate 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment (MCI) due to AD from normal cognition with areas under the curve of 0.984 and 0.881, respectively. The 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative diseases. Moreover, we identified 21 CSF and 18 serum stage-associated proteins reflecting AD stages. Our findings provide a foundation for developing blood-based tests for AD screening and staging in clinical practice.

Upregulation of Wnt2b exerts neuroprotective effect by alleviating mitochondrial dysfunction in Alzheimer's disease.

AIMS: This study investigated the relationship between plasma Wnt2b levels and Alzheimer's disease (AD), and explored the effect of Wnt2b on mitochondrial dysfunction in AD. METHODS: Healthy and AD subjects, AD transgenic mice, and in vitro models were used to investigate the roles of Wnt2b in abnormalities in canonical Wnt signaling and mitochondria in AD. RT-qPCR, immunoblotting, and immunofluorescence analysis were performed to assay canonical Wnt signaling. Mitochondrial structure was analyzed by electron microscopy. Flow cytometry was used to examine the intracellular calcium and neuronal apoptosis. RESULTS: Plasma Wnt2b levels were lower in AD patients and positively correlated with cognitive performance. Similarly, Wnt2b was reduced in the hippocampus of AD mice and in vitro models. Next, Wnt2b overexpression and recombinant Wnt2b were used to endogenously and exogenously upregulate Wnt2b levels. Upregulation of Wnt2b could effectively prevent downregulation of canonical Wnt signaling, mitochondrial dysfunction in in vitro AD models. Subsequently, intracellular calcium overload and neuronal damage were ameliorated. CONCLUSIONS: Our study highlights that Wnt2b decline is associated with cognitive impairment in AD, and upregulation of Wnt2b can exert neuroprotective effects in AD, particularly in ameliorating mitochondrial dysfunction.

Meloidogyne graminicola Population Structure in China Suggests a South-to-North Expansion.

The distribution range of root-knot nematode Meloidogyne graminicola is rapidly expanding, posing a severe threat to rice production. In this study, the sequences of cytochrome oxidase subunit I (COI) genes of rice M. graminicola populations from all reported provinces in China were amplified and sequenced by PCR. The distribution pattern and phylogenetic tree showed that all 54 M. graminicola populations in China have distinct geographical distribution characteristics; specifically, cluster 1 (southern China), cluster 2 (central south and southwest China), and cluster 3 (central and eastern China). The high haplotype diversity (Hd = 0.646) and low nucleotide diversity (π = 0.00682), combined with the negative value of Tajima's D (-1.252) and Fu's Fs (-3.06764), suggested that all nematode populations were expanding. The existence of high genetic differentiation (Fst = 0.5933) and low gene flow (Nm = 0.3333) indicated that there was a block of gene exchange between most populations. Mutation accumulation with population expansion might be directly responsible for the high genetic differentiation; therefore, the tested nematode population showed high within-group genetic variation (96.30%). The haplotype Hap8 was located at the bottom of the network topology, with the widest distribution and the highest frequency (59.26%), indicating that it was the ancestral haplotype. The populations in cluster 3 were newly invasive according to the lowest frequency of occurrence of Hap8, the highest number of endemic haplotypes, and the highest total haplotype frequency (60%). In contrast, cluster 1 having the highest genetic diversity (Hd = 0.772, π = 0.01127) indicated that it was the most primitive. Interestingly, the highest gene flow (Nm > 1), lowest genetic differentiation (Fst ≤ 0.33), and closest genetic distance (0.000) only occurred between the Guangdong/Hainan population and others, which suggested that there might be channels for gene exchange between them and that long-distance dispersal occurred. This suggestion is further confirmed by the weak correlation between genetic distance and geographical distance. Based on these data, a hypothesis can be drawn that M. graminicola populations in China were spreading from south to north, specifically from Guangdong and Hainan Provinces to other regions. Natural selection (including anthropogenic) and genetic drift were the main drivers of their evolution. Coincidentally, this hypothesis was consistent with the gradual warming trend and the chronological order of reporting these populations. The main factors influencing current M. graminicola population expansion and distribution patterns might be geography, climate, long-distance seedling transport, interregional operations of agricultural machinery, and rotation mode. It reminds human beings of the necessity to be vigilant about preventing nematode disease according to local conditions all year round.

NMDA Receptor GluN2B Subunit Is Involved in Excitotoxicity Mediated by Death-Associated Protein Kinase 1 in Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the most common form of neurodegenerative dementia among the elderly. Excitotoxicity has been implicated as playing a dominant role in AD, especially related to the hyperactivation of excitatory neurons. Death-associated protein kinase 1 (DAPK1) is a calcium/calmodulin-dependent kinase and involved in the pathogenesis of AD, but the roles and mechanisms of DAPK1 in excitotoxicity in AD are still uncertain. OBJECTIVE: We mainly explored the underlying mechanisms of DAPK1 involved in the excitotoxicity of AD and its clinical relevance. METHODS: Differentiated SH-SY5Y human neuroblastoma cells, PS1 V97 L transgenic mice, and human plasma samples were used. Protein expression was assayed by immunoblotting, and intracellular calcium and neuronal damage were analyzed by flow cytometry. Plasma DAPK1 was measured by ELISA. RESULTS: We found that DAPK1 was activated after amyloid-ß oligomers (AßOs) exposure in differentiated SH-SY5Y cells. Besides, we found the phosphorylation of GluN2B subunit at Ser1303 was increased, which contributing to excitotoxicity and Ca2+ overload in SH-SY5Y cells. Inhibiting DAPK1 activity, knockdown of DAPK1 expression, and antagonizing GluN2B subunits could effectively prevent AßOs-induced activation of GluN2B subunit, Ca2+ overload, and neuronal apoptosis. Additionally, we found that DAPK1 was elevated in the brain of AD transgenic mouse and in the plasma of AD patients. CONCLUSION: Our finding will help to understand the mechanism of DAPK1 in the excitotoxicity in AD and provide a reference for the diagnosis and therapy of AD.

Carnosic Acid Attenuates AßOs-Induced Apoptosis and Synaptic Impairment via Regulating NMDAR2B and Its Downstream Cascades in SH-SY5Y Cells.

Neuronal death and synaptic loss are principal pathological features of Alzheimer's disease (AD). Amyloid beta oligomers (AßOs) constitute the main neurotoxin underscoring AD pathology. AßOs interact with N-methyl-D-aspartate receptors (NMDARs), resulting in neurotoxic events, including activation of apoptosis and synaptic impairment. Carnosic acid (CA), extracted from Salvia rosmarinus, has been verified its neuroprotective effects in AD. However, the precise mechanisms by which CA induces synaptic protection remain unclear. In this study, we established an in vitro AD model using SH-SY5Y human neuroblastoma cells. We observed that CA improved neuronal survival by suppressing apoptosis. Moreover, CA restored synaptic impairments by increasing expression levels of brain-derived neurotrophic factor (BDNF), postsynaptic density protein-95 (PSD-95), and synaptophysin (Syn). Furthermore, we found these protective effects were dependent on inhibiting the phosphorylation of NMDAR subtype 2B (NMDAR2B), which further suppressed calcium overload and promoted activation of the extracellular signal-regulated kinase (ERK)-cAMP response element-binding protein (CREB) pathway. Administration of N-methyl-D-aspartic acid (NMDA), an agonist of NMDARs, abolished these effects of CA. Our findings demonstrate that CA exerts neuroprotective effects in an in vitro model of AD by regulating NMDAR2B and its downstream cascades, highlighting the therapeutic potential of CA as a NMDARs-targeted candidate in the treatment of AD.

CaMKIIα Signaling Is Required for the Neuroprotective Effects of Dl-3-n-Butylphthalide in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of neurodegenerative disease and most anti-AD drugs have failed in clinical trials; hence, it is urgent to find potentially effective drugs against AD. DL-3-n-butylphthalide (NBP) is a compound extracted from celery seed and is a multiple-target drug. Several studies have demonstrated the neuroprotective effects of NBP on cognitive impairment, but the mechanisms of NBP remains relatively unexplored. In this study, we found that NBP could alleviated the increase of intracellular Ca2+ and reversed down-regulation of Ca2+/calmodulin-dependent protein kinase alpha (CaMKIIα) signaling and rescued neuronal apoptosis in SH-SY5Y cells treated by Aß oligomers. However, these neuroprotective effects of NBP on neuronal damage and CaMKIIα signaling were abolished when CaMKIIα expression was knocked down or its activity was inhibited. Thus, our findings suggested that CaMKIIα signaling was required for the neuroprotective effects of NBP in AD and provided an improved basis for elucidating the mechanism and treatment of NBP in AD.

Decreased Levels of Insulin-Like Growth Factor-1 Are Associated with Alzheimer's Disease: A Meta-Analysis.

BACKGROUND: Alterations in levels of peripheral insulin-like growth factor-1 (IGF-1) in Alzheimer's disease (AD) have been reported in several studies, and results are inconsistent. OBJECTIVE: We conducted a meta-analysis to investigate the relationship between peripheral and cerebrospinal fluid IGF-1 levels and AD or mild cognitive impairment (MCI). METHODS: A systematic search in PubMed, Medline, Web of Science, Embase, and Cochrane Library was conducted and 18 studies were included. RESULTS: Results of random-effects meta-analysis showed that there was no significant difference between AD patients and healthy control (17 studies; standard mean difference [SMD], -0.01; 95%CI, -0.35 to 0.32) and between MCI patients and healthy control (6 studies; SMD, -0.20; 95%CI, -0.52 to 0.13) in peripheral IGF-1 levels. Meta-regression analyses identified age difference might explain the heterogeneity (p = 0.017). However, peripheral IGF-1 levels were significantly decreased in AD subjects (9 studies; SMD, -0.44; 95%CI, -0.81 to -0.07) and MCI subjects exhibited a decreasing trend (4 studies; SMD, -0.31; 95%CI, -0.72 to 0.11) in studies with sample size≥80. Cerebrospinal fluid IGF-1 levels also significantly decreased in AD subjects (3 studies; SMD, -2.40; 95%CI, -4.36 to -0.43). CONCLUSION: These findings suggest that decreased peripheral and cerebrospinal fluid IGF-1 levels might be a potential marker for the cognitive decline and progression of AD.

Toxic amyloid-ß oligomers induced self-replication in astrocytes triggering neuronal injury.

BACKGROUND: Soluble amyloid-ß oligomer (AßO) induced deleterious cascades have recently been considered to be the initiating pathologic agents of Alzheimer's disease (AD). However, little is known about the neurotoxicity and production of different AßOs. Understanding the production and spread of toxic AßOs within the brain is important to improving understanding of AD pathogenesis and treatment. METHODS: Here, PS1V97L transgenic mice, a useful tool for studying the role of AßOs in AD, were used to identify the specific AßO assembly that contributes to neuronal injury and cognitive deficits. Then, we investigated the production and spread of toxic Aß assemblies in astrocyte and neuron cultures, and further tested the results following intracerebroventricular injection of AßOs in animal model. FINDINGS: The results showed that cognitive deficits were mainly caused by the accumulation of nonameric and dodecameric Aß assemblies in the brains. In addition, we found that the toxic AßOs were duplicated in a time-dependent manner when BACE1 and apolipoprotein E were overexpressed, which were responsible for producing redundant Aß and forming nonameric and dodecameric assemblies in astrocytes, but not in neurons. INTERPRETATION: Our results suggest that astrocytes may play a central role in the progression of AD by duplicating and spreading toxic AßOs, thus triggering neuronal injury. FUND: This study was supported by the Key Project of the National Natural Science Foundation of China; the National Key Scientific Instrument and Equipment Development Project; Beijing Scholars Program, and Beijing Brain Initiative from Beijing Municipal Science & Technology Commission.

DAPK1: a Novel Pathology and Treatment Target for Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease and seriously damages the health of elderly population. Clinical drug research targeting at classic pathology hallmarks, such as amyloid-ß (Aß) and tau protein, failed to achieve effective cognitive improvement, suggesting that the pathogenesis of AD is much complicated, and there are still other unknown and undetermined important factors. Death-associated protein kinase 1 (DAPK1) is a calcium/calmodulin-dependent serine/threonine kinase that plays an important role in various neuronal injury models. Mounting evidence has demonstrated that DAPK1 variants are associated with AD risk. The activation of DAPK1 is also involved in AD-related neurodegeneration in the brain. Exploring the roles of DAPK1 in AD might help us understand the pathogenic mechanisms and find a novel promising therapeutic target in AD. Therefore, in this review, we comprehensively summary the main progress of DAPK1 in the AD studies from genetic risk, neuropathological process, and clinical potential implications.

Sulforaphane Inhibits the Generation of Amyloid-ß Oligomer and Promotes Spatial Learning and Memory in Alzheimer's Disease (PS1V97L) Transgenic Mice.

Abnormal amyloid-ß (Aß) aggregates are a striking feature of Alzheimer's disease (AD), and Aß oligomers have been proven to be crucial in the pathology of AD. Any intervention targeting the generation or aggregation of Aß can be expected to be useful in AD treatment. Oxidative stress and inflammation are common pathological changes in AD that are involved in the generation and aggregation of Aß. In the present study, 6-month-old PS1V97L transgenic (Tg) mice were treated with sulforaphane, an antioxidant, for 4 months, and this treatment significantly inhibited the generation and aggregation of Aß. Sulforaphane also alleviated several downstream pathological changes that including tau hyperphosphorylation, oxidative stress, and neuroinflammation. Most importantly, the cognition of the sulforaphane-treated PS1V97L Tg mice remained normal compared to that of wild-type mice at 10 months of age, when dementia typically emerges in PS1V97L Tg mice. Pretreating cultured cortical neurons with sulforaphane also protected against neuronal injury caused by Aß oligomers in vitro. These findings suggest that sulforaphane may be a potential compound that can inhibit Aß oligomer production in AD.

Genetics of vascular dementia - review from the ICVD working group.

BACKGROUND: Vascular dementia is a common disorder resulting in considerable morbidity and mortality. Determining the extent to which genes play a role in disease susceptibility and their pathophysiological mechanisms could improve our understanding of vascular dementia, leading to a potential translation of this knowledge to clinical practice. DISCUSSION: In this review, we discuss what is currently known about the genetics of vascular dementia. The identification of causal genes remains limited to monogenic forms of the disease, with findings for sporadic vascular dementia being less robust. However, progress in genetic research on associated phenotypes, such as cerebral small vessel disease, Alzheimer's disease, and stroke, have the potential to inform on the genetics of vascular dementia. We conclude by providing an overview of future developments in the field and how such work could impact patients and clinicians. CONCLUSION: The genetic background of vascular dementia is well established for monogenic disorders, but remains relatively obscure for the sporadic form. More work is needed for providing robust findings that might eventually lead to clinical translation.

Genome-wide miRNAs expression profiles of Schistosoma japonicum schistosomula in response to artesunate.

AIM: miRNAs play a significant role in pharmacogenomics and are likely to be important in the molecular mechanism of atesunate (ART) effects on Schistosoma japonicum. METHODS: We sequenced the RNAs using an Illumina (Solexa) DNA sequencer and compared the relative expression levels of the miRNAs in 10-day-old schistosomula from ART and the parallel control group. RESULTS: We characterized 95 known miRNAs from S. japonicum schistosomula individuals, including 38 novel miRNA families. Among the detectable 134 miRNAs differentially expressed (>2.0-fold change, p < 0.01) after ART treatment in schistosomula, a total of seven known or novel 3p- or 5p- derived S. japonicum miRNAs were characterized. We propose that sja-miR-125b may regulate the expression of ART metabolizing enzymes, glutathione synthetase or heme-binding protein 2 to help S. japonicum resists or adapts to drug stress and also ART may significantly inhibit sexual maturation of female worms mediated by mir-71b/2 miRNA cluster. CONCLUSION: This was the first comprehensive miRNAs expression profile analysis of S. japonicum in response to ART, and provides an overview of the complex network of the mechanism of action of ART on S. japonicum.

Association between vitamin D and development of otitis media: A PRISMA-compliant meta-analysis and systematic review.

BACKGROUND: Nutrients related to serum vitamin D level were previously shown to be significantly associated with the risk of many chronic diseases. This study aimed to assess potential relationships between serum vitamin D level and otitis media (OM) risk. METHODS: PubMed, EMBASE, and Cochrane Library databases were searched till Aug 18, 2015 for studies of quantitative OM risk estimates in relation to serum vitamin D level. The odds ratio and weighted mean difference, with 95% confidence intervals (CIs), were used to measure the relationship between serum vitamin D level and OM risk. RESULTS: Of the 89 articles identified by database search, 5 studies reported data of 16,689 individuals were included in our meta-analysis. We noted participants with OM was associated with lower level of plasma vitamin D when compared with patients without OM (weighted mean difference -5.67; 95% CI -8.08 to -3.26, P < 0.001). Furthermore, as compared with control group, serum vitamin D level was not associated with the risk of OM (odds ratio 0.80, 95% CI 0.47-1.38, P = 0.425). Subgroup analyses suggested that participants with acute OM might associate with lower serum vitamin D level. CONCLUSIONS: Plasma vitamin D level might play an important role on the progression of acute OM, whereas no significant impact in patients with chronic OM.

Overlap between Headache, Depression, and Anxiety in General Neurological Clinics: A Cross-sectional Study.

BACKGROUND: Many studies have reported that depression and anxiety have bidirectional relationship with headache. However, few researches investigated the roles of depression or anxiety in patients with headache. We surveyed the prevalence of depression and anxiety as a complication or cause of headache among outpatients with a chief complaint of headache at neurology clinics in general hospitals. Additional risk factors for depression and anxiety were also analyzed. METHODS: A cross-sectional study was conducted at 11 general neurological clinics. All consecutive patients with a chief complaint of headache were enrolled. Diagnoses of depression and anxiety were made using the Chinese version of the Mini International Neuropsychiatric Interview, and those for headache were made according to the International Classification of Headache Disorders, 2nd Edition. The headache impact test and an 11-point verbal rating scale were applied to assess headache severity and intensity. Logistic regression was used to analyze risk factors of patients with headache for depression or anxiety. RESULTS: A total of 749 outpatients with headache were included. Among them, 148 (19.7%) were diagnosed with depression and 103 (13.7%) with anxiety. Further analysis showed that 114 (15.2%) patients complaining headache due to somatic symptoms of psychiatric disorders and 82 (10.9%) had a depression or anxiety comorbidity with headache. Most patients with depression or anxiety manifested mild to moderate headaches. Poor sleep and severe headache-related disabilities were predictors for either depression or anxiety. CONCLUSION: Clinicians must identify the etiology of headache and recognize the effects of depression or anxiety on headache to develop specific treatments.

Brain Amyloid-ß Plays an Initiating Role in the Pathophysiological Process of the PS1V97L-Tg Mouse Model of Alzheimer's Disease.

Amyloid-ß (Aß) aggregation, tau hyperphosphorylation, oxidative stress, and neuroinflammation are major pathophysiological events in Alzheimer's disease (AD). However, the relationships among these processes and which first exerts an effect are unknown. In the present study, we investigated age-dependent behavioral changes and the sequential pathological progression from the brain to the periphery in AD transgenic (PS1V97L-Tg) mice and their wild-type littermates. We discovered that the brain Aß significantly increased at 6 months old, the increased brain Aß caused memory dysfunction, and the ability of Aß to induce tau hyperphosphorylation might be due to oxidative stress and neuroinflammatory reactions. The levels of Aß42, total tau (t-tau), oxidative stress parameters, and proinflammatory cytokines in plasma can be used to differentiate between PS1V97L-Tg mice and their wild-type littermates at different time points. Collectively, our findings support the hypothesis that Aß is a trigger among these pathophysiological processions and show that plasma biomarkers can reflect the condition of the AD brain.

Application of the IWG-2 Diagnostic Criteria for Alzheimer's Disease to the ADNI.

BACKGROUND: The International Working Group (IWG) recently proposed the revised diagnostic criteria for Alzheimer's disease (AD) to define and refine several types of AD, and to reclassify AD-related biomarkers into diagnostic and progression markers, but its performance is not known. OBJECTIVE: This study was designed to describe the application of the revised IWG criteria in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and to ascertain whether diagnostic and progression markers show significant differences in their relationships to AD severity and progression. METHODS: Based on the requirements of the refined criteria, 857 ADNI subjects with memory evaluation and at least one pathophysiological marker (CSF or amyloid imaging biomarkers) were eligible and reclassified in this study, and we calculated the associations of diagnostic (CSF and amyloid PET) and progression markers (MRI and fluorodeoxyglucose-PET) with AD severity and progression respectively. RESULTS: The majority (84.2% ) of ADNI AD group (n = 117) and 173 MCI (37.4% ) subjects in ADNI met the definition of typical AD; and 105 cognitively normal (41.0% ) individuals were diagnosed as asymptomatic AD. Furthermore, diagnostic and progression markers showed significant differences when correlated to AD severity and progression. CONCLUSION: A large proportion of AD dementia subjects were categorized as typical AD, and the revised criteria could identify typical AD from MCI status as well as asymptomatic AD at the asymptomatic stage. Moreover, the significant differences between diagnostic and progression markers further supported the new biomarkers categorization in the refined criteria.

[Design and Fabrication of Silver Nanoparticles/Graphen Complex Substrate and Its Application for Detecting Uranium (â ¥)].

Uranium is one of the important nuclear materials to nuclear industry. Because of the direct disposal of spent fuel, there is still a huge possibility that uranium migrates into the groundwater, causing water contamination. It is of great importance to understand the concentration and their species distribution in aqueous solutions. Surface-Enhanced Raman Scattering (SERS) technique has been widely used for the detection of uranium (Ⅵ). However, the interactions between uranium (Ⅵ) and SERS substrate cause the symmetric stretching vibration peak of uranium (Ⅵ) shift to low wave number direction, which is unfavorable for confirming the species of uranium (Ⅵ) in aqueous solution. For instance, the normal Raman bands of uranyl in nitric acid solution are 871 cm-1, which belongs to the symmetric stretching mode of UO2+2. However, it moves to 710 cm-1 on the surface of silver nanorods SERS substrtate. What's more, different SERS substrate causes different number of shift. Graphene has advantages of inertness and integrity as well as 2-dimensional thickness. In this paper, graphene-isolated SERS substrate which is silver nanoparticles (AgNPs)/graphene complex substrate, was designed to prevent the interaction between SERS substrate and it was analyzed by using the inert graphene layer. First of all, according to our previous work, AgNPs SERS substrate was fabricated on silicon wafer by using an ascorbic acid-actived self-assembly method. Then, AgNPs/graphene complex substrate was prepared by transfering monolayer graphene onto the self-assembly AgNPs substrate. The morphology of complex substrate was obtained by SEM. Some AgNPs link together closely to form nanochain structures. Nanochain structures were distributed evenly on the surface of silicon wafer. The 2-dimensional thickness of graphene did not affect the morphology of AgNPs. When using the complex substrate to detect uranyl nitrate (5×10-4 mol·L-1)，the Raman peak that appeared around 771 cm-1 is considered to be the symmetric stretching mode of UO2+2, shifting back about 52 cm-1 to high wave number direction when compared with AgNPs substrate, which was about ~719 cm-1. The result indicates that graphene layer isolates the interaction between AgNPs substrate and uranyl in some degree.