Publications by authors named "Colin Staab"
Loss-of-function variants in the lipid transporter ABCA7 substantially increase the risk of Alzheimer's disease, yet how they impact cellular states to drive disease remains unclear. Here, using single-nucleus RNA-sequencing analysis of human brain samples, we identified widespread gene expression changes across multiple neural cell types associated with rare ABCA7 loss-of-function variants. Excitatory neurons, which expressed the highest levels of ABCA7, showed disrupted lipid metabolism, mitochondrial function, DNA repair and synaptic signalling pathways.
View Article and Find Full Text PDFLoss-of-function (LoF) variants in the lipid transporter ABCA7 significantly increase Alzheimer's disease risk (odds ratio ≈ 2), yet the underlying pathogenic mechanisms and specific neural cell types affected remain unclear. To investigate this, we generated a single-nucleus RNA sequencing atlas of 36 human prefrontal cortex samples, including 12 carriers of ABCA7 LoF variants and 24 matched non-carriers. ABCA7 LoF variants were associated with transcriptional changes across all major neural cell types.
View Article and Find Full Text PDFArticle Synopsis
- Researchers have developed a cutting-edge brain-like 3D hydrogel model that mimics important aspects of human brain function, including neuron and immune cell interactions, to better study neurological diseases.
- This integrated model, called miBrain, includes all six major types of brain cells and demonstrates key features like neuronal activity, functional connectivity, and myelin production.
- The model is being used to investigate Alzheimer's disease, revealing how astrocytes might influence neuronal tau pathology and dysfunction through communication with microglia.