Cell-Cell Communication Patterns in Alzheimer's Disease Differ by Cortical Layer
- 1Emory University School of Medicine
Abstract
INTRODUCTIONExisting cell-cell communication (CCC) studies of Alzheimers 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).
METHODSWe 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.
RESULTSWe identified ADD/MCI-related CCC events with distinct patterns within cortical layers, including ADD-related interactions involving the known AD risk genes APOE and APP that were detected only in microglia in layer 5, and those with opposite effects of ADD and MCI in layers 5 and 6.
DISCUSSIONOur findings on cortical-layer-aware ADD/MCI-related CCC events underscore the importance of spatially-aware genomics studies of AD.
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BibTeX
@misc{dai2026cellcell,
title = {{Cell-Cell Communication Patterns in Alzheimer's Disease Differ by Cortical Layer}},
author = {Q. Dai and M. Murphy and J. Lyu and S. Tang and J. Hu and S. Tasaki and Y. Wang and D. A. Bennett and V. Menon and P. L. De Jager and A. S. Buchman and M. P. Epstein and J. Yang},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.05.26364776},
url = {https://www.medrxiv.org/content/10.64898/2026.10.05.26364776v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Cell-Cell Communication Patterns in Alzheimer's Disease Differ by Cortical Layer
AU - Q. Dai
AU - M. Murphy
AU - J. Lyu
AU - S. Tang
AU - J. Hu
AU - S. Tasaki
AU - Y. Wang
AU - D. A. Bennett
AU - V. Menon
AU - P. L. De Jager
AU - A. S. Buchman
AU - M. P. Epstein
AU - J. Yang
PY - 2026
DA - 2026/10/05
PB - medRxiv
DO - 10.64898/2026.10.05.26364776
UR - https://www.medrxiv.org/content/10.64898/2026.10.05.26364776v1
AB - INTRODUCTIONExisting cell-cell communication (CCC) studies of Alzheimers 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). METHODSWe 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. RESULTSWe identified ADD/MCI-related CCC events with distinct patterns within cortical layers, including ADD-related interactions involving the known AD risk genes APOE and APP that were detected only in microglia in layer 5, and those with opposite effects of ADD and MCI in layers 5 and 6. DISCUSSIONOur findings on cortical-layer-aware ADD/MCI-related CCC events underscore the importance of spatially-aware genomics studies of AD.
ER -