74 RESULTS
COMMENT It's great to see this. With these data, the lecanemab data, and the aducanumab data, we can see what treatments need to do to achieve efficacy. It looks also that earlier is better (and it may also be safer). Much practical work is required to get t
COMMENT I have never thought this paper was important, and I don’t think I have ever cited it. “Oligomer” toxicity has never been satisfactorily demonstrated in any system. It is too bad if these papers involve deceit, and journals and institutions need to crack
COMMENT My concern about this GWAS is that it is not a GWAS for Alzheimer’s disease but rather a GWAS for dementia. We know the diagnostic accuracy even in the highly cited clinic-based GWAS is only about 80 percent, and so is undoubtedly less in these GWAS which
COMMENT I think aducanumab had a small beneficial effect on mildly affected individuals. This opinion is weakly held, and I respect the opinion of those who disagree. We await further data for sure, as this did not reach the threshold of “beyond a reasonable doub
COMMENT a breakthrough, because plaque separation was extremely problematic. Years later, Konrad Beyreuther commented
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 l
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 dementi
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 transgeni
