“Integrated multimodal cell atlas of Alzheimer’s disease.”
Mariano I. Gabitto, et al. – Allen Institute for Brain Science.
To better understand cell type-specific changes in AD, this study analyzed how cell types in medial temporal gyrus change in number, gene expression, and gene availability over the disease time course. Innovations in tissue collection and processing allowed for probing post-mortem tissue from patients with advanced dementia at unprecedented depth. Changes in gene expression varied greatly across cell types, underscoring the need for cell type-specific assessments. SST+ interneurons were found to die off very early in disease progression, preceding cognitive symptoms, while layer 2/3 IT neurons and PVALB+ interneurons die off late in disease progression. Discovering why these subtypes are vulnerable, with SST+ interneurons the most vulnerable, is likely critical to understanding AD pathology.
This atlas will prove an invaluable resource for all future molecular studies of AD, especially those in cortex; similar studies of hippocampus will find common features and important differences in AD across affected brain regions.
To view the full paper, see our editor’s commentary, and add your own comments, go to the full paper in the DropCite Alzheimer’s Library.
