PubMed:28189700 JSONTXT

{"project":"Wangshuguang","denotations":[{"id":"T1","span":{"begin":509,"end":513},"obj":"B-Negative_Regulation"},{"id":"T2","span":{"begin":514,"end":516},"obj":"I-Negative_Regulation"},{"id":"T3","span":{"begin":517,"end":523},"obj":"I-Negative_Regulation"},{"id":"T4","span":{"begin":528,"end":539},"obj":"B-Molecular_Activity"},{"id":"T5","span":{"begin":602,"end":608},"obj":"B-Variation"},{"id":"T6","span":{"begin":621,"end":630},"obj":"B-Variation"},{"id":"T7","span":{"begin":640,"end":648},"obj":"B-Variation"},{"id":"T8","span":{"begin":663,"end":672},"obj":"B-Variation"},{"id":"T9","span":{"begin":716,"end":731},"obj":"B-Variation"},{"id":"T10","span":{"begin":743,"end":752},"obj":"B-Variation"},{"id":"T11","span":{"begin":843,"end":849},"obj":"B-Variation"},{"id":"T12","span":{"begin":1317,"end":1326},"obj":"B-Molecular_Activity"},{"id":"T13","span":{"begin":1327,"end":1330},"obj":"I-Molecular_Activity"},{"id":"T14","span":{"begin":1331,"end":1334},"obj":"I-Molecular_Activity"},{"id":"T15","span":{"begin":1335,"end":1342},"obj":"I-Molecular_Activity"},{"id":"T16","span":{"begin":1523,"end":1523},"obj":"B-Variation"}],"text":"CSF protein changes associated with hippocampal sclerosis risk gene variants highlight impact of GRN/PGRN.\nOBJECTIVE: Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs).\nMETHODS: Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes.\nRESULTS: The GRN risk SNP (rs5848) status correlated with variation in CSF proteins, with the risk allele (T) associated with increased levels of AXL Receptor Tyrosine Kinase (AXL), TNF-Related Apoptosis-Inducing Ligand Receptor 3 (TRAIL-R3), Vascular Cell Adhesion Molecule-1 (VCAM-1) and clusterin (CLU) (all p\u003c0.05 after Bonferroni correction). The TRAIL-R3 correlation was significant in meta-analysis with an additional dataset (p=5.05×10(-5)). Further, the rs5848 SNP status was associated with increased CSF tau protein - a marker of neurodegeneration (p=0.015). These data are remarkable since this GRN SNP has been found to be a risk factor for multiple types of dementia-related brain pathologies."}

{"project":"123123123","denotations":[{"id":"T1","span":{"begin":509,"end":513},"obj":"B-Negative_Regulation"},{"id":"T2","span":{"begin":514,"end":516},"obj":"I-Negative_Regulation"},{"id":"T3","span":{"begin":517,"end":523},"obj":"I-Negative_Regulation"},{"id":"T4","span":{"begin":528,"end":539},"obj":"B-Molecular_Activity"},{"id":"T5","span":{"begin":602,"end":608},"obj":"B-Variation"},{"id":"T6","span":{"begin":621,"end":630},"obj":"B-Variation"},{"id":"T7","span":{"begin":640,"end":648},"obj":"B-Variation"},{"id":"T8","span":{"begin":663,"end":672},"obj":"B-Variation"},{"id":"T9","span":{"begin":716,"end":731},"obj":"B-Variation"},{"id":"T10","span":{"begin":743,"end":752},"obj":"B-Variation"},{"id":"T11","span":{"begin":843,"end":849},"obj":"B-Variation"},{"id":"T12","span":{"begin":1317,"end":1326},"obj":"B-Molecular_Activity"},{"id":"T13","span":{"begin":1327,"end":1330},"obj":"I-Molecular_Activity"},{"id":"T14","span":{"begin":1331,"end":1334},"obj":"I-Molecular_Activity"},{"id":"T15","span":{"begin":1335,"end":1342},"obj":"I-Molecular_Activity"},{"id":"T16","span":{"begin":1523,"end":1523},"obj":"B-Variation"}],"text":"CSF protein changes associated with hippocampal sclerosis risk gene variants highlight impact of GRN/PGRN.\nOBJECTIVE: Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs).\nMETHODS: Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes.\nRESULTS: The GRN risk SNP (rs5848) status correlated with variation in CSF proteins, with the risk allele (T) associated with increased levels of AXL Receptor Tyrosine Kinase (AXL), TNF-Related Apoptosis-Inducing Ligand Receptor 3 (TRAIL-R3), Vascular Cell Adhesion Molecule-1 (VCAM-1) and clusterin (CLU) (all p\u003c0.05 after Bonferroni correction). The TRAIL-R3 correlation was significant in meta-analysis with an additional dataset (p=5.05×10(-5)). Further, the rs5848 SNP status was associated with increased CSF tau protein - a marker of neurodegeneration (p=0.015). These data are remarkable since this GRN SNP has been found to be a risk factor for multiple types of dementia-related brain pathologies."}