Paper
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Lau SF, Cao H, Fu AK, Ip NY. Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer's disease. Proc Natl Acad Sci U S A. 2020 Oct 13;117(41):25800-25809. Epub 2020 Sep 28 PubMed.
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Comments
Mass General Institute for Neurodegenerative Disease
Single-cell RNA-Seq studies are an incredible resource for the field, but they don’t always represent the full diversity of cell types in the brain. This study from Lau et al. nicely captures an endothelial cell population and adds insight to gene-expression changes occurring in AD vasculature. With data increasingly highlighting vascular dysfunction as an integral component of AD pathology, these results could help identify molecular targets to improve cerebrovascular health and combat detrimental changes, such as impaired perfusion and blood-brain barrier leakiness.
I’m thrilled that this human data supports our own observations of tau-overexpressing mice, in which we also observed an angiogenesis-related gene-expression signature. How this ties in exactly with what we know from histological studies is unclear since the field is equivocal about whether or not neovascularization or endothelial cell loss occurs in Alzheimer’s.
It would be great to visualize some of these transcripts in situ and see if there are any obvious morphological changes or local alterations in plasma protein leakage. Also, it will be important going forward to know if these endothelial gene-expression changes vary across brain regions and if they are specific to Alzheimer’s.
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