Glial changes and gene expression in Alzheimer's disease from snRNA-Seq and spatial transcriptomics

Area of Science:

• Neuroscience
• Genomics
• Pathology

Background:

• Alzheimer's disease (AD) is marked by brain atrophy and neuron loss, but large-scale cellular change data is limited.
• Key brain regions like the prefrontal cortex and temporal gyrus are vulnerable to AD neuropathological changes (ADNC).

Purpose of the Study:

• To quantify cellular alterations in AD using integrated single-nuclei sequencing and spatial transcriptomics.
• To analyze gene expression changes and their links to AD pathology, including APOE and Lewy bodies.

Main Methods:

• Integrated single-nuclei sequencing (SEA-AD) and spatial transcriptomics of human brain tissue.
• Differential gene expression analysis, cell proportion assessment, and pathway analysis.

Main Results:

• RORB-expressing neurons remained stable despite vulnerability to ADNC.
• Astrocytes showed increased reactivity, cytokine signaling, and oxidative stress, with reduced synaptic support.
• Microglia exhibited heightened immune surveillance and phagocytic activity.

Conclusions:

• Glial cells, especially astrocytes and microglia, play critical roles in Alzheimer's disease progression.
• Findings offer insights into cellular dynamics and potential glial-targeted therapies for AD.