A single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer’s disease

Endothelial cells are enriched in genes associated with genetic risk for AD

Our analyses were based on data from 77 cortical brain samples from donors with AD (n = 41) or non-diseased controls (NDC, n = 36). Three different datasets were analysed jointly: two of the datasets included nuclei from samples in which fluorescence-activated sorting (FACS) was performed to remove neuronal and oligodendrocyte nuclei before barcoding and sequencing. This achieved a better representation of the less abundant vascular cell types of interest^21,22. The third dataset included EC obtained by a dextran gradient-based enrichment of lightly dissociated cells to select for microvessel-associated nuclei.

After integration of the FACS-enriched datasets using LIGER²³, cells were clustered and represented in a UMAP²⁴ (Fig. 1A). AD and NDC donor nuclei and nuclei from different datasets, brain…