Exploring Cellular Heterogeneity: Single-Cell and Spatial Transcriptomics of Alzheimer Disease Brains and iPSC-Derived Microglia.

Background: Substantial evidence has established the critical role of microglia, the brain's resident immune cells, in the pathogenesis of Alzheimer's disease (AD). Microglia exhibit diverse transcriptional states in response to neuroinflammatory stimuli, and understanding these states is crucial for elucidating the underlying mechanisms of AD.

Methods: In this work, we integrated single-cell and spatially resolved transcriptomics data from multiple cohorts and brain regions, including microglia from experimental and human brains.

Single-cell atlas of healthy human blood unveils age-related loss of NKG2CGZMBCD8 memory T cells and accumulation of type 2 memory T cells.

Extensive, large-scale single-cell profiling of healthy human blood at different ages is one of the critical pending tasks required to establish a framework for the systematic understanding of human aging. Here, using single-cell RNA/T cell receptor (TCR)/BCR-seq with protein feature barcoding, we profiled 317 samples from 166 healthy individuals aged 25-85 years old. From this, we generated a dataset from ∼2 million cells that described 55 subpopulations of blood immune cells.

Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy.

Extracellular deposition of amyloid-β as neuritic plaques and intracellular accumulation of hyperphosphorylated, aggregated tau as neurofibrillary tangles are two of the characteristic hallmarks of Alzheimer's disease. The regional progression of brain atrophy in Alzheimer's disease highly correlates with tau accumulation but not amyloid deposition, and the mechanisms of tau-mediated neurodegeneration remain elusive. Innate immune responses represent a common pathway for the initiation and progression of some neurodegenerative diseases.