2010
DOI: 10.1371/journal.pone.0013950
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Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease

Abstract: BackgroundLate Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes.MethodologyWe applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings w… Show more

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Cited by 367 publications
(298 citation statements)
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“…Extending these leads, Jones et al (2010) have assessed the functional role of SNPs not quite reaching genomewide significance in AD and arrived at a very similar conclusion, i.e. that especially pathways related to immune system response and lipid metabolism appear to be particularly overrepresented [58]. More recently, rare amino-acid changing variants in TREM2 (encoding for the triggering receptor located on myeloid cells 2) have been implicated as additional risk factors for LOAD [59,60].…”
Section: Sporadic Ad/loadmentioning
confidence: 95%
See 1 more Smart Citation
“…Extending these leads, Jones et al (2010) have assessed the functional role of SNPs not quite reaching genomewide significance in AD and arrived at a very similar conclusion, i.e. that especially pathways related to immune system response and lipid metabolism appear to be particularly overrepresented [58]. More recently, rare amino-acid changing variants in TREM2 (encoding for the triggering receptor located on myeloid cells 2) have been implicated as additional risk factors for LOAD [59,60].…”
Section: Sporadic Ad/loadmentioning
confidence: 95%
“…Functionally, these genes appear to be mostly linked with three (interdependent) molecular pathways: (I) the amyloidogenic cascade, (II) cholesterol-lipid metabolism, and (III) immune-inflammatory mechanisms [57]. Extending these leads, Jones et al (2010) have assessed the functional role of SNPs not quite reaching genomewide significance in AD and arrived at a very similar conclusion, i.e. that especially pathways related to immune system response and lipid metabolism appear to be particularly overrepresented [58].…”
Section: Sporadic Ad/loadmentioning
confidence: 99%
“…There is extensive functional and clinical evidence that immune dysfunction plays a key role in the pathogenesis of the relapse‐remitting phase of MS 20, 21. For AD, Yokoyama et al22 showed that eight variants were associated with both AD and immune‐mediated diseases, and there is further evidence from pathway analysis1, 23, 24 and from animal models 25. For PD, the role of the immune system has been suggested through pathway analyses,26, 27 animal models,28 and variants in the Human Leukocyte Antigen (HLA) region reaching statistical significance in GWASs 3, 29.…”
Section: Introductionmentioning
confidence: 99%
“…However, for those which can be considered essentially polygenic, involving hundreds or thousands of variants, it is intuitively likely that multiple independent risk factors will exist within related sets of genes, and even within individual genes. 9,10 Such a nonrandom dispersion of association signals among annotated gene sets has been empirically demonstrated in, for example, Crohn's disease and Bipolar disorder, 11 and this has already been exploited to provide insights into the broad mechanisms underlying a number of phenotypes, including Alzheimer's disease 13 and height. 5 Moreover, the latter 5 confirmed the hypothesis that a large number of loci have multiple independently associated variants.…”
Section: Introductionmentioning
confidence: 99%