Systematic analysis of cellular cross-talk reveals a role for SEMA6D-TREM2 regulating microglial function in Alzheimer's disease.

ABSTRACT: Cellular cross-talk, mediated by membrane receptors and their ligands, is crucial for brain homeostasis and can contribute to neurodegenerative diseases such as Alzheimer's disease (AD). To find cross-talk dysregulations involved in AD, we reconstructed cross-talk networks from single-nucleus transcriptional profiles of 67 clinically and neuropathologically well-characterized controls and AD brain donors from the Knight Alzheimer Disease Research Center and the Dominantly Inherited Alzheimer Network cohorts. We predicted a role for TREM2 and additional AD risk genes mediating neuron-microglia cross-talk in AD. We identified a gene network mediating neuron-microglia cross-talk through TREM2 and neuronal SEMA6D, which we predicted is disrupted in late AD stages. Using spatial transcriptomics

SUBMITTER: D'Oliveira Albanus R 

PROVIDER: S-EPMC12766863 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature