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Dani N, Herbst RH, McCabe C, Green GS, Kaiser K, Head JP, Cui J, Shipley FB, Jang A, Dionne D, Nguyen L, Rodman C, Riesenfeld SJ, Prochazka J, Prochazkova M, Sedlacek R, Zhang F, Bryja V, Rozenblatt-Rosen O, Habib N, Regev A, Lehtinen MK. A cellular and spatial map of the choroid plexus across brain ventricles and ages. Cell. 2021 Apr 27; PubMed.
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Washington University in St. Louis, School of Medicine
This is an exciting story from Wyss-Coray’s lab, as now we finally have a beautiful atlas of endothelial and stromal cells from human brain and meninges.
The diversity of the populations and the changes they observe with AD are very interesting. The fact that many of the AD-associated genes are expressed in endothelial cells, whereas in mice these are more in microglial cells, is another interesting aspect of the paper. We may not fully understand yet what this means, but these results are fascinating enough to dig deeper. I must also note that the new method that was developed here to sequence endothelial cells (VINE-Seq) is pretty remarkable.
View all comments by Jonathan KipnisKU Leuven
This is a very interesting and thorough paper. They authors describe a massive database of single-cell transcriptomes of AD patients and controls. I much appreciate how they focus on the vasculature, an aspect that does not get enough attention yet, more specifically, in most human AD single-cell studies coming out these days. It is interesting to see that a large number of potentially relevant AD risk genes express in the brain vasculature, and that some of them even differentially express in AD.
However, as with all papers of this scope, we only get to see the tip of the iceberg. I would be very interested to see a deeper analysis of the impact of carrying APOE4 on the gene-expression alterations in AD, in particular in the light of the AD risk genes, as all these aspects are now treated separately.
Just as other papers omit cells from the vasculature, this paper depletes non-vasculature cells, hence I’m not fully convinced of their conclusion that many AD GWAS risk genes actually enrich in the vasculature. However, these results do shed a different light on many AD-relevant genes, including well-known ones such as APOE and PICALM.
A further strong point of the paper is the effort the authors make to highlight the differences between mouse and humans, and to emphasize the care we need to take to interpret results derived from mouse experiments in the light of Alzheimer’s disease.
All combined, I think this is an important paper for the field.
View all comments by Mark FiersMake a Comment
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