Year: 2026
Type: preprint
Abstract: INTRODUCTION: Existing cell-cell communication (CCC) studies of Alzheimer's disease dementia (ADD) using cortical snRNAseq data do not account for the distinct cell-type and gene-expression profiles within cortical layers. Cortical-layer-aware CCC analysis may clarify biological mechanisms associated with ADD and mild cognitive impairment (MCI). METHODS: We applied our recent analytical tool STACCato to identify CCC events associated with ADD and MCI within cortical layers, using a large-scale prefrontal cortex snRNAseq dataset (∼1.4M nuclei, n=395) with cortical layers annotated from reference spatial transcriptomics data. RESULTS: that were detected only in microglia in layer 5, and those with opposite effects of ADD and MCI in layers 5 and 6. DISCUSSION: Our findings on cortical-layer-aware ADD/MCI-related CCC events underscore the importance of spatially-aware genomics studies of AD.
Source: medRxiv
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Epidemiologic Study of Neural Reserve and Neurobiology of Aging, Risk Factors, Pathology, and Clinical Expressions of AD, Rush Alzheimer's Disease Core Center, Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targets, Rush Alzheimer's Disease Research Center
OpenAlex ID: W7220953175