6 research outputs found
New insights into the genetic etiology of Alzheimer's disease and related dementias
- Author
- Aaltonen L.
- Aaltonen V.
- Aarsland Dag
- Aavikko M.
- Abalos M.S.
- Abdelnour Carla
- Abner E.
- Abraham R.
- Adams H.
- Adams P.M.
- Adarmes-GĂłmez A.
- Adarmes-GĂłmez A.D.
- Aguilera N.
- Aguilera N.
- Aguirre A.
- Ahmad S.
- Akinyemi R.O.
- Al-Chalabi A.
- AlarcĂłn-MartĂn Emilio
- Albert M.S.
- Albin R.L.
- Alcolea Daniel
- Alegret Montserrat
- Ali M.
- Allen M.
- Allende I.R.
- Alonso M.D.
- Alonso M.D.
- Alvarez I.
- Alvarez L.
- Amer-Ferrer G.
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- Amouyel Philippe
- Anastasiou A.
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- Publication venue
- Publication date
- 01/01/2022
- Field of study
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE Δ4 allele
Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial
- Author
- Publication venue
- 'BMJ'
- Publication date
- 30/09/2014
- Field of study
OBJECTIVES\nTo evaluate safety and efficacy of weekly (qw) and every other week (q2w) dosing of sarilumab, a fully human anti-interleukin 6 receptor α (anti-IL-6Rα) monoclonal antibody, for moderate-to-severe rheumatoid arthritis (RA).\nMETHODS\nIn this dose-ranging study, patients (n=306) with active RA, despite methotrexate, were randomly assigned to placebo or one of five subcutaneous doses/regimens of sarilumab: 100â
mg q2w, 150â
mg q2w, 100â
mg qw, 200â
mg q2w, 150â
mg qw for 12â
weeks, plus methotrexate. The primary end point was ACR20 at Week 12. Secondary endpoints included ACR50, ACR70, Disease Activity Score in 28 joints (C reactive protein). Safety, pharmacokinetics, pharmacodynamics and efficacy in population subgroups were assessed.\nRESULTS\nThe proportion of patients achieving an ACR20 response compared with placebo was significantly higher for sarilumab 150â
mg qw (72.0% vs 46.2%, multiplicity adjusted p=0.0203). Higher ACR20 responses were also attained with 150â
mg q2w (67%; unadjusted (nominal) p=0.0363) and 200â
mg q2w (65%; unadjusted p=0.0426) versus placebo. Sarilumab â„150â
mg q2w reduced C reactive protein, which did not return to baseline between dosing intervals. Infections were the most common adverse event; none were serious. Changes in laboratory values (neutropenia, transaminases and lipids) were consistent with reports with other IL-6Rα inhibitors.\nCONCLUSIONS\nSarilumab improved signs and symptoms of RA over 12â
weeks in patients with moderate-to-severe RA with a safety profile similar to reports with other IL-6 inhibitors. Sarilumab 150â
mg and sarilumab 200â
mg q2w had the most favourable efficacy, safety and dosing convenience and are being further evaluated in Phase III.Pathophysiology and treatment of rheumatic disease
EFFECT OF PROCESSING PARAMETERS ON THE TEMPERATURE AND MOISTURE CONTENT OF MICROWAVE-BLANCHED PEANUTS
- Author
- Publication venue
- 'Wiley'
- Publication date
- Field of study
Sarilumab Plus Methotrexate in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results of a Phase III Study
- Author
- Publication venue
- 'Wiley'
- Publication date
- 30/06/2015
- Field of study
Pathophysiology and treatment of rheumatic disease
Sarilumab Plus Methotrexate in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate Results of a Phase III Study
- Author
- Publication venue
- 'Wiley'
- Publication date
- 30/06/2015
- Field of study
Pathophysiology and treatment of rheumatic disease
New insights into the genetic etiology of Alzheimerâs disease and related dementias
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Characterization of the genetic landscape of Alzheimerâs disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/âproxyâ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE Δ4 allele. © 2022, The Author(s)