69 RESULTS
COMMENT It is great to see new putative genetic risk loci. Two issues: Are these new genetic risk loci certain? And how much of the genetic risk has been found? On the first point: The power of “simple GWAS” is that the statistical test is easy to understand. Its ...
COMMENT The beauty of standard genome-wide association studies is the simplicity of the analysis pipeline … a high (p) value is required for Bonnferroni correction, but, once that is past, the result is credible and reproducible. However, the very high correction ...
COMMENT One should always be aware that this is a single case report. It remains possible there are other reasons for this woman’s protection. However, there are precedents for other APOE variants that change risk of AD (Kamboh et al., 1999; Medway et al., 2014). ...
COMMENT This study involves mostly the same samples analysed in a previous study (Pittman et al., 2005). A general problem in genetic studies is that often the same samples end up in many different studies, and this makes it difficult to assess whether something ...
COMMENT I would like to see this replicated. The proposed associations with PD and ALS were not correct. With small numbers and rare variants this is often a tough study to do and repeat and there will be a tendency for only positive reports to make it into the ...
COMMENT My concern about this work is that I find it difficult to square with the occurrence of Alzheimer’s disease in all Down's syndrome and in all carriers of some APP and PSEN mutations. The authors in their introduction bring up the idea of “slow virus” ...
COMMENT This work clearly confirms the work of Holstege and colleagues showing that loss-of-function variants in SORL1 are associated with a large increase in risk of AD. These mutations confer very high risk that can be considered close to penetrant. The authors ...
COMMENT Jansen et al. and Marioni et al. add new samples to the established Alzheimer GWAS, and by that means they increase the (n) of these studies and lead to the provisional identification of new loci for the disease. Both studies use family history of ...
COMMENT The connection between lysosome dysfunction and Parkinson’s disease is now clear. These papers—as well as one this week by Schapira in Brain and another due out soon from Shulman, Heutink, and the IPDGC—show clearly that lysosome dysfunction, going beyond ...
COMMENT I think this is an extremely important and insightful piece of work, which firmly puts the microglial response as key to Alzheimer pathogenesis. It builds on the work of Jones et al. (2010), as well as our own work and on both human genetics and ...
COMMENT Replications are important in medical science, and this study essentially replicates the paper from deCode on this Alzheimer-protective mutation published five years ago. This replication is particularly important because its result points at a ...
COMMENT This paper from the De Strooper lab convincingly shows that there is not a clear effect of PLD3 on APP biology and reignites the debate on whether PLD3 is an AD gene (Cruchaga et al., 2013). Genetic analysis looking for rare variants is subject to ...
COMMENT It is clear that neuroimmune response is key to the genetics of Alzheimer’s disease, not just because of the identification of TREM2 as a risk locus but also from the systematic analysis of the GWAS hits (Jones et al., 2010). Interestingly, transgenic ...
COMMENT De Strooper and Karran’s thoughtful review takes us past the initiating events in AD, to think about the entirety of the pathogenesis. With all the new genetic risk factors we have discovered, this is an entirely appropriate development. We have been ...
COMMENT I agree with Sam Sisodia that assessing the structure of other mutations would be useful. An obvious one is the D9 mutation which has a clear effect on function (Perez-Tur et al., 1995; Thinakaran et al., 1996). J.Hardy 0 A mutation in Alzheimer's ...
