New insights into the genetic etiology of Alzheimer's disease and related dementias.

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 ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

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 ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

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 ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Effects of levosimendan on left ventricular functional remodelling and exercise intolerance: a tissue Doppler study

Levosimendan is a calcium sensitizer that demonstrates enhanced myocardial contractility. There is little information concerning the effect of levosimendan on left ventricular tissue parameters and exercise capacity. We evaluated the effects of a 24-h course of levosimendan therapy on cardiac tissue parameters in 30 patients, aged 48 - 70 years, admitted to our hospital for the management of decompensated heart failure. All patients underwent echocardiographic examination using tissue Doppler imaging (TDI) and a 6-min walk test. Systolic myocardial velocity of the mitral annulus (Sm) was significantly increased in levosimendantreated patients compared with placebotreated patients. There was a positive correlation between Sm and exercise capacity. Levosimendan might be expected to increase cardiac contractile force, especially Sm velocity, in parallel with exercise tolerance. The study has also shown that the progress of ventricular function after levosimendan treatment in patients with exercise intolerance could be monitored effectively by Sm velocity measurements using TDI

Discrimination between physiologic and pathologic left ventricular dilatation

The identification of certain cardiovascular disease in athletes may constitute the basis for disqualification from competition in an effort to minimize the risk of sudden cardiac death. The aim of this study was to assess diastolic and systolic parameters measured by tissue Doppler imaging in endurance veteran athletes who had prominent cardiac dilatation and patients with idiopathic dilated cardiomyopathy in order to determine whether these variables might differentiate each other. (c) 2005 Elsevier Ireland Ltd. All rights reserved

33 Questions about Triglycerides and Cardiovascular Effects: Expert Answers [33 Soruda Trigliseritler ve Kardiyovasküler Etkileri: Uzman Yanıtları]

PubMed ID: 28446733[No abstract available

The WHO global alliance against chronic respiratory diseases in Turkey (GARD Turkey)

In order to prevent and control non-communicable diseases (NCDs), the 61st World Health Assembly has endorsed an NCD action plan (WHA resolution 61.14). A package for essential NCDs including chronic respiratory diseases (CRDs) has also been developed. The Global Alliance against Chronic Respiratory Diseases (GARD) is a new but rapidly developing voluntary alliance that is assisting World Health Organization (WHO) in the task of addressing NCDs at country level. The GARD approach was initiated in 2006. GARD Turkey is the first comprehensive programme developed by a government with all stakeholders of the country. This paper provides a summary of indicators of the prevalence and severity of chronic respiratory diseases in Turkey and the formation of GARD Turkey